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Chimeric antigen receptor generations. First generation CARs include a single-chain variable region from a monoclonal antibody paired with an intracellular signaling domain, the CD3 z chain from the CD3 TCR or FcR g . Second and third generation CARs include an additional one or two co-stimulating domains (e.g. CD28, 4-1BB, OX-40) that increase signal strength and persistence, with increased proliferation and cytokine production. TM: transmembrane domain; H: heavy chain; L: light chain. (A color version of this figure is available in the online journal.)
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In the past 50 years, disease burden has steadily shifted from infectious disease to cancer. Standard chemotherapy has long been the mainstay of cancer medical management, and despite vast efforts towards more targeted and personalized drug therapy, many cancers remain refractory to treatment, with high rates of relapse and poor prognosis. Recent d...
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... safer alternative to other targets for adoptive TCR therapy, with a decreased risk of ‘‘on-target, off-tumor’’ effects. However, when TCR therapy against NY-ESO-1 was used in patients with synovial cell carcinoma and melanoma, the clinical results were mixed. One year after therapy, two of 11 patients with melanoma had complete tumor regression, and one patient with synovial cell carcinoma mounted a partial response. 44 Fortunately, there was no toxicity associated with the transferred cells. Because CTAs are highly specific to cancer cells, they were expected to be a safer target for TCR therapy. However, highly specific CTA expression on target cells only decreases the chances of an on-target, off-tumor event. If the affinity-enhanced TCR cross-reacts with a distinct, albeit similar, antigen expressed in normal tissue, then an ‘‘off-target, off-tumor event’’ is possible. Off-target, off- tumor effects are very concerning because they progress rapidly, with potentially lethal consequences, and are notoriously hard to predict. For instance, melanoma-asso- ciated antigen 3 (MAGE-A3) is a CTA that is specifically expressed in more than 30% of common epithelial malignancies, including melanoma, breast, lung, esophageal, and head and neck cancers. 45 In a TCR study targeting the MAGE-A3 antigen, two patients undergoing treatment experienced cardiogenic shock, resulting in death. Autopsy revealed severe myocardial damage and histo- pathological analysis revealed T-cell infiltration. Alarmingly, despite preclinical screening for cross- reactivity, MAGE-A3 was found to have a similar structure to a human cardiac protein, Titin, suggesting that the TCR-modified T-cell mistook a Titin-derived peptide on cardiomyocyte MHCs for MAGE-A3. In the follow-up, the TCR-modified T-cells reacted in vitro with beating human cardiomyocytes, thus confirming that Titin was the cross reactive protein. 46 In short, in the MAGE-A3 TCR trial, an off-target, off-tumor event led to the fatal destruction of cardiac tissue in the two patients. 47 Off-target, off-tumor toxicity is fast progressing and devastating. As evidenced by the MAGE-A3 trial, off- target, off-tumor effects are hard to completely rule out in preclinical studies due to variable protein sequence hom- ology between animal models and humans. As a result, it is far more difficult to identify potential off-target, off-tumor effects than it is to determine on-target off-tumor effects. This is as relevant to CAR applications as it was for TCR therapy for solid tumors. In order for CAR therapy targeting CTAs or other TAAs to succeed in the clinic, the risk of off-target off-tumor effects needs to be addressed using various safety strategies. For example, prior to a clinical trial, in-vitro studies could use human genome data to synthesize and test candidate cross reactive proteins for reactivity. Additionally, future CAR safety studies could potentially deploy high-throughput proteomics to screen for cross-reactivity with the selected tumor-specific antigens, to test off-target off-tumor anti- genic candidates, or even to select for the safest epitope. Another potentially advantageous safety strategy would be to include small molecule-inducible suicide switches in the modified T-cells. 48 Finally, perhaps the best conceptual approach in terms of therapeutic safety would be to use mRNA-modified T-cells in CAR applications. The CAR mRNA modifying the T-cell would be short-lived and would degrade a short time after infusion, allowing for enhanced dosage control and a safer therapy. As previously discussed, CARs consist of an antigen- derived binding motif, linked with a hinge to transmembrane and intracellular signaling domains, the latter derived from the z chain of CD3 or the FcR receptor g chain. In other words, CAR T-cells do not require MHC-mediated recogni- tion of the target antigen, allowing for a far greater range of potential cellular targets. Furthermore, modified CAR T- cells have increased power relative to TCR-based therapies, as they are immune to down-regulation of MHC expression in neoplastic cells. The correlate is that, by bypassing the MHC, CAR T-cells can only target cell surface markers. It is important to note that CAR affinity for the target epitope is a key determinant of CAR therapy efficacy. A murine antibody single chain variable fragment (Fv) is articulated to the transmembrane domain via a hinge region, which allows for greater flexibility of the antigen-receptor config- uration. Since CAR T-cells are not MHC-restricted, their interaction with antigen presenting cells (APCs) is limited, and they do not receive a co-stimulatory signal from an APC. Indeed, whereas first generation CAR design consists of the CAR fused to the intracellular portion of the TCR domain, second generation CAR design includes one co-stimulatory domain, e.g. CD28 or 4-1BB, and third generation CARs include two or more co-stimulatory signaling domains, e.g. CD28 and 4-1BB (Figure 3). The first successful CAR therapies were directed against hematologic cancers, notably B-cell malignancies. B-cell ablation is considered safe for patients in the context of the prompt recovery of other blood counts. For that reason, the CD19 marker, highly specific to B-cells including those transformed to lymphoma and leukemia, was chosen as target for CAR T-cell therapy. The first CAR targeting CD19 was dramatically effective in a patient with B-cell lymphoma, with eradication of B-lineage cells for a prolonged period of time, with concomitant marked lymphoma regression. 49 In order to further strengthen CAR T-cell activation, a co- stimulatory domain from CD137 (4-1BB) was added in a subsequent trial for advanced B-cell chronic lymphocytic leukemia (CLL), with two out of three patients undergoing complete remission. CAR-modified T-cell lines successfully expanded ex vivo more than 1000-fold, engrafted in the bone marrow and could establish CAR memory for at least six months. 50 The combination of a CAR with a co-stimulatory signal led to a robust response: each CAR-expressing T-cell was estimated to lyze at least 1000 CLL cells. 50 Consequently, tumor lysis syndrome was reported as common serious adverse event in both CLL and B-cell acute lymphoid leukemia (AML) trials. 51,52 The lesson was that, during CAR therapy, patients need to be closely monitored for signs of tumor lysis syndrome since CAR T-cells ablate large amounts of target cells at levels vastly superior to those of past immunotherapies. CAR T-cell therapy has succeeded where conventional therapies have failed, and CAR T-cell therapy has led to remission in patients with refractory disease. In a landmark clinical trial, autologous T-cells transduced with a CD19- directed CAR led to a 90% remission rate (27/30 cases) for patients with relapsed or refractory acute lymphoblastic leukemia (ALL), including 15 patients for whom stem cell transplantation had previously failed. 2 The six-month event-free survival rate was 67%; overall survival rate was 78%. All patients experienced cytokine-release syndrome, with severe cytokine-release syndrome observed in 27% of patients. Severe cases of cytokine-release syndrome were associated with a higher tumor burden and were treated effectively with tocilizumab, the anti-IL-6 receptor antibody. The results of this trial were without precedent and demonstrated that CAR T-cells can overcome mechanisms of B-cell neoplasm resistance in subsets of patients with abysmally low prognosis. Indeed, 90% remission was a quasi-reversal of the odds for these patients, and firmly made the case that CAR therapy, if done correctly, can completely upend longstanding cancer treatment paradigms, providing hope for millions of patients with dire prognosis. Although CAR T-cell therapy was first attempted against a solid tumor, CAR therapy for solid tumors has seen limited progress due to safety concerns. In a 2008 neuroblastoma trial, Epstein-Barr virus (EBV)-specific T-cells were engineered to also co-express a CAR targeted at diasialoganglio- side GD2, an antigen expressed by neuroblastoma cells. 53 Half the patients (4/8) had evidence of tumor regression. Intriguingly, the virus-specific CAR T-cells survived longer than T-cells with CAR alone. Additionally, on-target, off-tumor toxicity is an especially critical safety concern for CAR therapy, even more so than for TCR therapy because CAR T-cell destruction of cells is not MHC- mediated, leading to a stronger and faster response during activation. For instance, a CAR therapy derived from a mAb against carboxyanhydrase-IX (CAIX), a marker of clear cell renal cell carcinoma, also destroyed normal bile duct epithelial cells, which happened to also express CAIX. 53 It was a striking example of an on-target, off-tumor effect in a CAR therapy, and a potent reminder that future CAR strategies will need to further guarantee targeting specificity. 53 The power of CAR therapy resides in the ability to choose any surface marker as a target, and to hit that target with high efficacy. Nonetheless, not all patients respond completely to CAR therapy and the mechanisms of failure will need to be defined in non-responding patients. For instance, the chimeric murine mAb Fv presents the risk of immunogenicity, potentially resulting in CAR neutraliza- tion. Tumor antigen loss and the development of antigen variants could lead to tumor resistance to CAR therapy. Another challenge is the development of treatment-related toxicity, cytokine-release syndrome, which has been linked to massive macrophage and IL-6 activation. Although IL-6 blockade has been successful in managing the most severe manifestations of cytokine-release syndrome, regulating the level or dose of CAR expression would allow for greater control over toxicity as well. CAR T-cell therapy targeting CD19 risks selecting for neoplastic clones that express low or no CD19. 52 Beyond absence of CD19, dynamic or cyclical CD19 ...
Citations
... First generation CARs were characterised by an extracellular domain containing a single-chain variable factor (scFv) serving as an antigen binding moiety (derived from the immunoglobulin variable regions of heavy and light chains), as well as an intracellular domain containing a CD3ζ chain to initiate T cell activation. However, first generation CARs yielded insufficiently durable T cell responses in vivo (Firor et al., 2015), which was overcome with the addition of either one or two costimulatory domains in the second and third generation CARs, respectively, to recapitulate physiological T cell responses (e.g. CD28, CD134 or CD137) (Savoldo et al., 2011;Cappell and Kochenderfer, 2021). ...
... The intracellular signaling domain of CAR T-cells determines the strength, quality, and persistence of a T-cell response to tumor antigens and is frequently manipulated to enhance the potency of CAR T-cell therapy [33]. So, the incorporation of both the primary and costimulatory signaling domains, CD28, CD134, and CD137 in a single gene product will enhance the persistence and efficacy of T-cells against tumors [23] by enhancing T-cell proliferation, glucose metabolism, and self-limited T-cell persistence, with CD28 + and stimulation of lipid oxidation and support greater T-cell persistence with 4-1BB [34]. ...
Bacterial Clustered Regularly Inter Spaced Palindromic Repeats (CRISPR) Associated proteins in association with a short guide RNA discovered as a bacterial adaptive immunity in the 20th century nowadays became a breakthrough gene editing tool in the arena of biomedical science and bioengineering. Historically, it was first identified as how bacteria maintain its genome integrity through a targeted endonuclease of any exogenous invading genetic elements either from plasmid or viruses by storing a memory of the first infection, expression of spacers and interference. Recognizing how it works, humans nowadays, are able to reprogram it using computer databases and genetic engineering knowledge and tools to cut and edit the genome at a targeted site for cancer therapy, viral therapy, and gene disruption for bioengineering purposes. They were also able to deactivate its endonuclease properties and making it only bind to the target site and act as a reporting signal in cooperation with other chemicals to indicate the presence of the genome so that it is being used as a diagnostic procedure for several diseases. However, the role of the system in repairing the broken DNA is unexplained or null. So in this detailed review, the historical discoveries, the mechanisms, processes, challenges and future research focus of the CRISPR/CaS9 how the system will be harnessed and un erroneously repairs the introduced break are discussed.
... The most recent and sophisticated iteration has shown improved treatment efficacy and reduced toxicity [27]. Due to the lack of costimulatory molecules (CM) and cytokines, first-generation CAR T-cells (1G CAR-Ts) show poor survival and proliferation in the body, resulting in a lack of anti-tumor effects, making their use obsolete [28,29]. The study in metastatic neuroblastoma that expressed high levels of CD171 (L1-cell adhesion molecule) targeted with CE7R -CAR-CD8 + on six patients with 12 infusions showed no toxicity for normal nervous tissue but the effect on tumor cells [30]. ...
Chimeric Antigen Receptor (CAR) based therapies are becoming increasingly important in treating patients. CAR-T cells have been shown to be highly effective in the treatment of hematological malignancies. However, harmful therapeutic barriers have been identified, such as the potential for graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome (CRS). As a result, CAR NK-cell therapy is expected to be a new therapeutic option. NK cells act as cytotoxic lymphocytes, supporting the innate immune response against autoimmune diseases and cancer cells by precisely detecting and eliminating malignant cells. Genetic modification of these cells provides a dual approach to the treatment of AD and cancer. It can be used through both CAR-independent and CAR-dependent mechanisms. The use of CAR-based cell therapies has been successful in treating cancer patients, leading to further investigation of this innovative treatment for alternative diseases, including AD. The complementary roles of CAR T and CAR NK cells have stimulated exploration in this area. Our study examines the latest research on the therapeutic effectiveness of these cells in treating both cancer and ADs.
... CARs can bind directly to lipids, proteins, and carbohydrates, expanding the range of cell surface targets [136]. The first generation of CARs only included the CD3ζ signaling domain, which was fused with extracellular single-chain antibodies to modify and activate T cells [137]. However, the short survival time of these cells meant that they could not effectively activate T cells. ...
Immune microenvironment and immunotherapy have become the focus and frontier of tumor research, and the immune checkpoint inhibitors has provided novel strategies for tumor treatment. Malignant pleural effusion (MPE) is a common end-stage manifestation of lung cancer, malignant pleural mesothelioma and other thoracic malignancies, which is invasive and often accompanied by poor prognosis, affecting the quality of life of affected patients. Currently, clinical therapy for MPE is limited to pleural puncture, pleural fixation, catheter drainage, and other palliative therapies. Immunization is a new direction for rehabilitation and treatment of MPE. The effusion caused by cancer cells establishes its own immune microenvironment during its formation. Immune cells, cytokines, signal pathways of microenvironment affect the MPE progress and prognosis of patients. The interaction between them have been proved. The relevant studies were obtained through a systematic search of PubMed database according to keywords search method. Then through screening and sorting and reading full-text, 300 literatures were screened out. Exclude irrelevant and poor quality articles, 238 literatures were cited in the references. In this study, the mechanism of immune microenvironment affecting malignant pleural effusion was discussed from the perspectives of adaptive immune cells, innate immune cells, cytokines and molecular targets. Meanwhile, this study focused on the clinical value of microenvironmental components in the immunotherapy and prognosis of malignant pleural effusion.
... Chimeric antigen receptor (CAR) T-cell therapy is a novel cell-based immunotherapy that has attracted considerable attention from researchers and healthcare professionals due to its outstanding therapeutic efficacy (1). Unlike major histocompatibility complex (MHC)-dependent T-cell receptors (TCRs), CAR can recognize antigens from any MHC background, allowing CAR T cells to target tumor cells that achieve immune evasion through down regulation of MHC expression or impaired proteasome antigen processing (2,3). ...
The high expression of CD7 targets in T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoma has attracted considerable attention from researchers. However, because CD7 chimeric antigen receptor (CAR) T-cells undergo fratricide, CD7 CAR T-cells develop an exhaustion phenotype that impairs the effect of CAR T-cells. There have been significant breakthroughs in CD7-targeted CAR T-cell therapy in the past few years. The advent of gene editing, protein blockers, and other approaches has effectively overcome the adverse effects of conventional methods of CD7 CAR T-cells. This review, in conjunction with recent advances in the 64th annual meeting of the American Society of Hematology (ASH), provides a summary of the meaningful achievements in CD7 CAR T-cell generations and clinical trials over the last few years.
... CAR-T cells are functionally divided into three functional regions ( Figure 1) [2]. One of these, the extracellular structural domain, consists of a single variable chain fragment (scFv) responsible for recognizing and binding monoclonal antibodies to antigens and a hinge region that plays a linking role. ...
... The T-cellspecific co-stimulatory molecule 4-1BB or CD28 is found in an activation domain. The T-cell receptor CD3ζ also possesses an intracellular signaling domain [2]. ...
The problem of cancer is becoming more and more serious. As of 2021, the global of cancer patients has reached 14 million. Now how to treat cancer has become one of the key research topics. To treat cancer, people have found many cure methods, like salvage chemotherapy, radiotherapy, cytotoxic chemotherapy, and so on. But these therapies can only delay the patient's life. They cannot cure cancer. People want to find a therapy to completely empty the cancer cells. Until 1989, scientists have found a way to engineer T-cell called Chimeric antigen receptor T cell (CAR-T) to attack cancer cells, CAR-T therapy now has four generations. Good results have been achieved in the treatment of B-cell malignant lymphoma. However, CAR-T treatment in the area of solid tumors now still has many challenges. Therefore, the topic of this article is based on this structure of CAR-T cells, The development of CAR-T cell therapies and clinical application of CAR-T to reveal advantages and disadvantages of CAR-T treatment in cancer.
... The principal differences among the CAR generations consist of specific costimulatory molecules. The first generation contains only the CD3ζ signaling end domain, whose linking with the extracellular scFv modifies and activates T cells [33]. However, due to its short survival time and incomplete T-cell activation, it was necessary to conceive a second and third generation of CARs, which include one or two additional costimulatory molecules (respectively), such as CD27, CD28, 41BB, ICOS, and OX-40. ...
Simple Summary
To date, different therapeutic strategies, including immunotherapies, have been shown to prolong survival in breast cancer patients, representing one of the most common malignancies. Our article deals with chimeric antigen receptor-based immunotherapy in breast cancer.
Abstract
Breast cancer represents one of the most common tumor histologies. To date, based on the specific histotype, different therapeutic strategies, including immunotherapies, capable of prolonging survival are used. More recently, the astonishing results that were obtained from CAR-T cell therapy in haematological neoplasms led to the application of this new therapeutic strategy in solid tumors as well. Our article will deal with chimeric antigen receptor-based immunotherapy (CAR-T cell and CAR-M therapy) in breast cancer.
... Over the last decade, research in cancer immunotherapy has made significant progress in the treatment of cancer and resulted in dramatic improvements in patient survival [1][2][3][4][5][6]. Chimeric antigen receptor (CAR)-T cells, generated by modifying human autologous or allogeneic T cells to target specific antigens, are shown to have promising response rates in hematologic malignancies and offer durable efficacy [7][8][9][10]. ...
... Searches were conducted on Pub-Med and Embase in May 2022. A total of seven searches were conducted on each database: [1] "CAR" or "chimeric antigen receptor", [2] "CAR-T cell" and "acute lymphoblastic leukemia" or "ALL", [3] "CAR-T cell" and "diffuse large B-cell lymphoma" or "DLBCL", [4] "CAR-T cell" and "multiple myeloma" or CAR" or "MM", [5] "chimeric antigen receptor" and "acute lymphoblastic leukemia", [6] "chimeric antigen receptor" and "diffuse large B-cell lymphoma", and [7] "chimeric antigen receptor" and "multiple myeloma". ...
... All clinical prospective and retrospective studies reporting outcomes in adult patients (age ≥ 18 years) with hematologic malignancies including Acute Lymphoblastic Leukemia (ALL), Diffuse Large B-cell Lymphoma (DLBCL) and Multiple Myeloma (MM) met the inclusion criteria for consideration. Studies were excluded if they met any of the following exclusion criteria: [1] Articles reported in languages other than English, [2] Conference presentations and abstracts, [3] Studies that did not use lymphodepletion regimen, [4] Studies in children, [5] Studies in solid tumors, [6] Studies using bispecific CAR-T cells, [7] Studies using CAR-T cell cocktails, [8] Studies using bispecific antibodies, [9] Studies using antibody drug conjugates, [10] Articles reporting additional outcomes/post hoc analyses of previously published study, [11] Preclinical studies, [12] Systematic literature review articles, and [13] Review articles. Bispecific CAR-T cells, solid tumors and studies in children, which are expected to have widely different kinetics, and comparatively different efficacy and safety, are excluded from the review. ...
CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity are concerning. Our goal is to assess CAR-T cell clinical trial publications to address the question of whether administration of CAR-T cells as dose fractions reduces toxicity without adversely affecting efficacy. Systematic literature review of studies published between January 2010 and May 2022 was performed on PubMed and Embase to search clinical studies that evaluated CAR-T cells for hematologic cancers. Studies published in English were considered. Studies in children (age < 18), solid tumors, bispecific CAR-T cells, and CAR-T cell cocktails were excluded. Data was extracted from the studies that met inclusion and exclusion criteria. Review identified a total of 18 studies that used dose fractionation. Six studies used 2-day dosing schemes and 12 studies used 3-day schemes to administer CAR-T cells. Three studies had both single dose and fractionated dose cohorts. Lower incidence of Grade ≥ 3 CRS and neurotoxicity was seen in fractionated dose cohorts in 2 studies, whereas 1 study reported no difference between single and fractionated dose cohorts. Dose fractionation was mainly recommended for high tumor burden patients. Efficacy of CAR-T cells in fractionated dose was comparable to single dose regimen within the same or historical trial of the same agent in all the studies. The findings suggest that administering dose fractions of CAR-T cells over 2-3 days instead of single dose infusion may mitigate the toxicity of CAR-T cell therapy including CRS and neurotoxicity, especially in patients with high tumor burden. However, controlled studies are likely needed to confirm the benefits of dose fractionation.
... In first generation, endo-domain (intracellular signaling motif) is comprised of only CD3-ζ chain that provides insufficient T-cell proliferation and cytokine production. 23 Therefore, in second generation, an intracellular costimulatory domain (CD28 or 4-1BB) has been added in order to ameliorate T-cell proliferation and persistence. 24,25 In third generation, both CD28 and 4-1BB have been added intracellularly in order to further increase T-cell proliferation and persistence. ...
Over the last decade, the emergence of several novel therapeutic approaches has changed the therapeutic perspective of human malignancies. Adoptive immunotherapy through chimeric antigen receptor T cell (CAR‐T), which includes the engineering of T cells to recognize tumor‐specific membrane antigens and, as a result, death of cancer cells, has created various clinical benefits for the treatment of several human malignancies. In particular, CAR‐T‐cell‐based immunotherapy is known as a critical approach for the treatment of patients with hematological malignancies such as acute lymphoblastic leukemia (ALL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and non‐Hodgkin's lymphoma (NHL). However, CAR‐T‐cell therapy of hematological malignancies is associated with various side effects. There are still extensive challenges in association with further progress of this therapeutic approach, from manufacturing and engineering issues to limitations of applications and serious toxicities. Therefore, further studies are required to enhance efficacy and minimize adverse events. In the current review, we summarize the development of CAR‐T‐cell‐based immunotherapy and current clinical antitumor applications to treat hematological malignancies. Furthermore, we will mention the current advantages, disadvantages, challenges, and therapeutic limitations of CAR‐T‐cell therapy. The chimeric antigen receptor T‐cells (CAR‐T) are engineered T cells that recognize tumor‐specific membrane antigens, and cause death of cancer cells. This approach has created various clinical benefits for the treatment of several human hematological malignancies.
... As our understanding of T-cell activation and tumor microenvironment (TME) improves, the structures of CARs are becoming more complex ( Figure 3) (26)(27)(28)(29). The intracellular signaling domains of the first-generation CARs had no costimulatory molecules and include only CD3ζ, which is fused with the extracellular single-chain antibody scFv to modify and activate T cells (30). However, after the specific antigens recognize tumor cells, the proliferative capacity, persistence, and cytotoxicity of the first-generation CARs becomes suboptimal. ...
Background and objective:
In recent years, adoptive cell therapy (ACT) has shown great potential in antitumor treatment. To significantly improve the clinical efficacy of ACT against solid tumors, we may need to carefully study the latest developments in ACT. As one of the most common malignancies, colorectal cancer (CRC) is a major risk to human health and has become a significant burden on global healthcare systems. This article reviews the recent advances in the treatment of CRC with ACT.
Methods:
We searched PubMed for articles related to ACT for CRC published as of August 31, 2022, and retrieved relevant clinical trial information on the National Institutes of Health ClinicalTrials.gov website. Based on search results, comprehensive and systematic review is made.
Key content and findings:
This article provides an overview of the research progress of ACT for CRC, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR)-engineered T-cell therapy, and tumor-infiltrating lymphocyte (TIL) therapy. Common tumor-associated antigens (TAAs) in clinical trials of CAR-T cell therapy for CRC are described.
Conclusions:
Despite many obstacles, ACT shows great promise in treating CRC. Therefore, more basic experimental studies and clinical trials are warranted to further clarify the effectiveness and safety of ACT.
