Adi Diab's research while affiliated with University of Texas MD Anderson Cancer Center and other places

Publications (39)

Article
Purpose: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated anti-tumor activity in preclinical models. The ILLUMINATE-101 phase 1 study explored the safety, dose, efficacy, and immune effects of intra-tumoral (it) tilsotolimod monotherapy in multiple solid tumors. Methods: Patients with a diagn...
Article
Full-text available
Hepatocellular carcinoma (HCC) represents the second most common cause of cancer-related deaths and accounts for over eighty percent of primary liver cancers worldwide. Surgical resection and radiofrequency ablation in small tumors are included in the treatment options for HCC patients with good liver function profiles. According to the Milan Crite...
Article
Finding biomarkers for predicting anti-tumor responses and immune-related adverse events (irAEs) with immune checkpoint therapy remains a challenge. Lozano et al. have developed a composite biomarker score that includes the frequency of effector-memory CD4 T cells and TCR clonality of CD4 T cells in peripheral blood as a potentially predictive biom...
Article
Many patients with advanced melanoma are resistant to immune checkpoint inhibition. In the ILLUMINATE-204 phase 1/2 trial, we assessed intratumoral tilsotolimod, an investigational Toll-like receptor 9 agonist, with systemic ipilimumab in patients with anti-PD-1-resistant advanced melanoma. In all patients, 48.4% experienced grade 3/4 treatment-eme...
Chapter
Cancer treatment has been fully transformed with the development of cancer immunotherapies. The progress in the understanding of the immune system has led to the development of monoclonal antibodies targeted against regulatory immune checkpoints, which control T-cell activation. These therapies produce an antitumor response characterized by constan...
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Background Immune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GV...
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Background Image guided intra-tumor administration of investigational immunotherapeutic agents represents an expanding field of interest. We present a retrospective review of the safety, feasibility & technical nuances of real-time image guidance for injection & biopsy across a spectrum of extracranial solid malignancies utilizing the discipline of...
Article
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Background Immune checkpoint inhibitors (ICIs) have resulted in unprecedented advances in the treatment of cancer. By disinhibiting the immune system, they enhance anti-tumor immunity, but provoke off-target inflammatory and immune-related adverse events (irAEs) which can seriously impact morbidity and mortality. The exact immunobiology of irAEs is...
Article
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Background NKTR-262 is a small-molecule agonist of toll-like receptors (TLR) 7/8. Given by intratumoral (IT) injection, NKTR-262 is retained within the tumor microenvironment (TME) and promotes an immunostimulatory milieu and tumor antigen release. Bempegaldesleukin (BEMPEG) is a CD122-preferential IL-2 pathway agonist, which increases proliferatio...
Article
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Background Management of certain immune mediated adverse events (irAEs) can be challenging and may require prolonged/chronic immune suppression with corticosteroids or other immunosuppressant which could compromise and even reverse the efficacy of immune checkpoint inhibitors (ICI). While the exact immunobiology of irAEs is not fully understood the...
Article
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Background Autoimmunity is associated with increased risk of malignancy. However, patients with pre-existing autoimmune diseases (AIDs) were excluded from immune checkpoint inhibitor (ICI) trials as these agents can cause immune-related adverse events (irAEs). Data are limited on the safety and efficacy of combination immunotherapy in this at-risk...
Article
Background Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has shown great benefit in patients with melanoma. 1,2 It was suggested that long term tumor immunosurveillance is provided by TIL persisting after transfer. Dendritic cells (DC) are professional antigen presenting cells and have the ability to optimally ac...
Article
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Background An unmet need exists for novel therapies that produce deep and durable responses in more patients with metastatic melanoma (metMEL). Encouraging clinical activity was observed with the CD122-preferential IL-2 pathway agonist bempegaldesleukin(BEMPEG) plus nivolumab(NIVO) in first-line metMEL in the phase 1/2 PIVOT-02 trial ( NCT02983045...
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Following publication of the original article [1], the authors reported an error in the Acknowledgments section. It should be read: ‘We are grateful to Mohsin Shah from the Department of Emergency Medicine at The University of Texas MD Anderson Cancer Center for assisting in study selection, and to Gregory F. Pratt from the Research Medical Library...
Article
Background: Preclinical evidence suggests that low-dose radiation may overcome the inhibitory effects of the tumor stroma and improve a tumor's response to immunotherapy, when combined with high-dose radiation to another tumor. The aim of this study was to evaluate tumor responses to this combination in a clinical setting. Methods: A post-hoc an...
Article
Background: Although immune-related thyroiditis (irT) with immune checkpoint inhibitors (ICI) is a common consequence, its natural course and management recommendations are not well characterized in existing guidelines. We sought to study the evolution of irT and describe its course and sequelae. Methods: Retrospective study of cancer patients t...
Article
Purpose: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monot...
Article
Full-text available
Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs...
Article
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Pre-clinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-PD-1 immunotherapy (n=112). Significant differences were observed in the di...
Conference Paper
Background Immune checkpoint inhibitors (CPIs) have significantly improved outcomes for patients with various cancers. However, CPIs are associated with immune-related adverse events (irAEs). Two to three percent of patients receiving a CPI develop arthritis. In general, severe irAEs are treated with a high-dose steroid and a tumor necrosis factor...
Article
136 Background: Checkpoint inhibitors (CPI) have transformed melanoma treatment but many patients remain refractory. CPI plus i.t. IMO may improve response by activating innate immune function. Based on this we initiated a trial of IMO in combination with ipi or pembrolizumab (pem) in RM. Methods: Adults with RM that progressed during or after ≥ 12...
Article
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Purpose: Little prospective data is available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiation therapy (SABR) with ipilimumab. Experimental design: SABR was given either concurrently (1 day after the first dose) or sequentia...
Article
Immune checkpoint inhibitors (anti–cytotoxic T-lymphocyte antigen 4 and anti programmed cell death 1/programmed cell death 1 ligand antibodies) have shown impressive clinical activity in multiple cancer types. Despite achieving great clinical success, challenges and limitations of these drugs as monotherapy or various combinational strategies inclu...
Article
Background: In pts with ESBC, cryo combined with cytotoxic T-lymphocyte antigen 4 blockade was well tolerated and did not delay standard-of-care mastectomy. As observed in mice, cryo+ipi may liberate tumor-associated antigens, synergistically activate tumor-reactive T-cells, and confer long-term anti-tumor immunity. Because singular biomarkers of r...
Article
Full-text available
With the recent success of checkpoint inhibitors and other immunomodulating agents, there has been renewed interest in the combination of such agents with radiation. The biologic premise behind such a strategy is that the tumor-antigen release achieved by localized radiation will promote specific tumor targeting by the adaptive immune system, which...
Article
Background: Intratumoral cryo combined with immune modulation generates a potent systemic anti-tumor immune response that might improve recurrence free survival in ESBC. In this study, we evaluate the safety of pre-op cryo and/or ipi (10mg/kg) in pts with ESBC. Radiographic correlates and intratumoral/serologic immune responses are also explored. M...
Article
Background: Trastuzumab (H) has improved outcomes for patients with HER2 overexpressing (HER2+) breast cancer (BC) and thus increased the at-risk period for development of brain metastases (BM). In this study we describe the characteristics and outcomes of patients with HER2+BCBM who underwent stereotactic radiosurgery (SRS) or whole brain radiatio...
Article
Background: With cryoablation, probes are inserted into tumors to induce crystallization, osmotic changes, vascular stasis, and ultimately tumor necrosis. The resultant release of tumor antigens could activate a tumor-specific immune response through antigen presentation by dendritic cells (DC) to T-cells. Cryoablation is an effective treatment mod...
Article
2599 Background: The carbohydrate antigen sLea, recognized by the monoclonal antibody (mAb), CA19-9, is commonly expressed on breast cancer cells and is a potential target for vaccine therapy. Methods: The primary endpoints were safety and immunogenicity. Secondary endpoint was presence of circulating tumor cells (CTC) pre and post injection. Pts r...

Citations

... In the last decade, the transplant oncology field has been evolving and advances in locoregional and systemic therapies including immunotherapy have provided additional options for further exploration of neoadjuvant and adjuvant strategies to improve HCC resection rates [6,7,[13][14][15][16][17][18][19][20][21][22][23][24][25]. We report an interesting case of a patient with HCC who developed pseudo-progression followed by an excellent response with significant downstaging after neoadjuvant treatment with atezolizumab plus bevacizumab. ...
... The disease control rate (DCR) was 71.4%. Overall, 48% of patients had ≥ grade 3 toxicities [1]. However, in the phase II ILLUMINATE-301 trial, the combination of tilsotolimod plus ipilimumab failed to meet the primary endpoint of improved ORR versus ipilimumab alone (8.8% vs 8.6%) in patients with advanced melanoma who are refractory to a PD-1 inhibitor [2]. ...
... Although there was no increase in the risk of acute or chronic GVHD in the pembrolizumab group, seven of nine patients received only one dose of pembrolizumab prior to allo-SCT, which may not have been enough exposure to elicit post-SCT complications [45]. These results are consistent with numerous other studies that have shown the safety of consolidative allo-SCT after ICIs in both AML and MDS, especially with the use of post-transplantation cyclophosphamide prophylaxis [46][47][48]. ...
... There was no difference in survival between the arms. The median PFS was 3.6 months in the TIL arm and 7.2 months in the TIL+ dendritic cell arm, while the median OS was 4.1 years in the TIL arm and 2 years in the TIL + dendritic cell arm (130). ...
... In the first in-humanPhase I trial, bempegaldesleukin demonstrated durable antitumor efficacy in patients with pretreated advanced or metastatic solid tumors.32 Bempegaldesleukin in combination with nivolumab received breakthrough therapy designation by the FDA for patients with untreated unresectable or metastatic melanoma following the Phase I/II PIVOT-02 trial, which reported a 53% overall response rate and a 34% complete response rate,33 with the greatest responses seen among patients with PD-L1 expressing tumors. A Phase III trial (PIVOT IO 001) evaluating bempegaldesleukin in combination with nivolumab compared to nivolumab alone as first-line therapy for patients with advanced melanoma is currently ongoing (NCT03635983) (Table 2). ...
... Moreover, clinical data with NKTR-262 (TLR7/8 agonist) and bempegaldesleukin (NKTR-214, PEGylated aldesleukin) show that the combination is well-tolerated and has PD activity. 37 The antitumor efficacy of TransCon IL-2 β/γ monotherapy in mice was statistically significant, while the overall tumor growth inhibition was quite modest compared with what has been reported for other IL-2 variants. 13 20 38 39 Unlike cynomolgus IL-2Rs that bind human IL-2 with similar affinity/potency as the human counterparts, and unlike mouse IL-2Rα which maintains good affinity to human IL-2, mouse IL-2Rβ has substantially lower potency for human IL-2. ...
... Tilsotolimod is a potent TLR9 agonist with demonstrated clinical activity in patients with advanced melanoma refractory to PD-(L)1 inhibition. On-treatment tumor biopsies from patients treated with tilsotolimod in combination with either ipilimumab or pembrolizumab in a phase I dose escalation study (NCT02644967) demonstrated maturation of myeloid DC1 subsets and an IFN-α response gene signature in both injected and uninjected tumors [87]. Additionally, higher CD4+ and CD8+ T cell proliferation rates were observed in tumor biopsies from responding patients. ...
... 89 This result just accords with the role of low-dose RT in patients who receive SBRT combined with IO, which better facilitates the abscopal effect and increases the occurrence rate in patients with metastatic disease in iRT. 280 Moreover, RT induces the production and release of cytokines. The most important mechanism is to activate the cGAS-STING and NF-κB signaling leading to an increase of cytokines. ...
... Nivolumab caused the most graft rejections (52%), whereas ipilimumab and pembrolizumab showed an inferior rate (25% and 26.7%) [130]. In another study by Abdel-Wahab et al. involving 37 patients (mostly suffering from melanoma), graft loss after ICIs therapy was 81% and death was reported in 46% of patients [131]. ...
... Hyperthyroidism and hypothyroidism are the two most common thyroid dysfunctions (TDs) in patients treated with ICIs. Generally, TD often manifests as an early onset of transient thyrotoxicosis, followed by hypothyroidism [16]. Several studies reported that 10-20% of lung cancer patients would have TD during ICIs treatment. ...