Benjamin Rengstl

BioNTech Cell & Gene Therapies GmbH · Immunoreceptor Therapy

The oncofetal antigen Claudin 6 (CLDN6) is highly and specifically expressed in many solid tumors, and could be a promising treatment target. We report dose escalation results from the ongoing phase 1/2 BNT211-01 trial evaluating the safety and feasibility of chimeric antigen receptor (CAR) T cells targeting the CLDN6 with or without a CAR-T cell-a...

Novel therapies are needed to for the treatment of atypical teratoid/rhabdoid tumor (ATRT), an aggressive brain tumor that predominantly affects young children and has an average 5-year survival under 50%. Claudin-6 (CLDN6) is a tight junction protein present during development and is expressed in up to 70% of ATRT specimens but not in normal tissu...

2518 Background: We are developing a chimeric antigen receptor (CAR)-T cell therapy targeting claudin 6 (CLDN6), an oncofetal antigen that is undetectable in healthy somatic tissue and highly expressed in various solid cancers. Autologous CLDN6 CAR-T cells are being tested alone and in combination with CLDN6-encoding CAR-T cell Amplifying RNA Vacci...

INTRODUCTION Novel therapies for atypical teratoid/rhabdoid tumor (ATRT) are desperately needed. Claudin-6 (CLDN6) is a tight junction protein present during early development and in some tumors, but not at appreciable levels in normal tissue. CLDN6-targeted chimeric antigen receptor (CAR) T cells with a CAR-T cell–amplifying RNA vaccine have demon...

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive brain tumor that predominantly affects young children and has an average 5-year survival under 50%. Novel, targeted therapies are desperately needed. Claudin 6 (CLDN6) is a tight junction protein present during development and expressed in up to 70% of ATRT specimens but not in normal tissue,...

Chimeric antigen receptor (CAR) T cells are efficacious in patients with B-cell malignancies, while their activity is limited in patients with solid tumors. We developed a novel heterodimeric TCR-like CAR (TCAR) designed to achieve optimal chain pairing and integration into the T-cell CD3 signaling complex. The TCAR mediated high antigen sensitivit...

Background: BNT211 comprises two drug products, a chimeric antigen receptor (CAR)-T cell product candidate that targets the tumor specific antigen claudin 6 (CLDN6) and a CAR-T cell-Amplifying RNA Vaccine (CARVac). In mice, CARVac mediates expansion of adoptively transferred CAR-T cells, improving their persistence and functionality. BNT211 aims to...

Background BNT211 is a chimeric antigen receptor (CAR)-T cell product candidate that targets the tumor specific antigen Claudin-6 (CLDN6). Preclinical studies demonstrated that combining these engineered cells with a CAR-T cell Amplifying RNA Vaccine (CARVac) leads to in vivo expansion of adoptively transferred CAR-T cells, resulting in their impro...

Chimeric antigen receptor (CAR)-T cells have shown efficacy in patients with B cell malignancies. Yet, their application for solid tumors has challenges that include limited cancer-specific targets and nonpersistence of adoptively transferred CAR-T cells. Here, we introduce the developmentally regulated tight junction protein claudin 6 (CLDN6) as a...

A one-two, CAR-T cell punch Chimeric antigen receptor (CAR)–T cells have been clinically effective in killing certain hematological malignancies, but achieving long-term patient responses for solid tumors remains a challenge. Reinhard et al. describe a two-part “CARVac” strategy to overcome poor CAR-T cell stimulation and responses in vivo. They in...

The mechanisms involved in malignant transformation of mature B and T lymphocytes are still poorly understood. In a previous study, we compared gene expression profiles of the tumor cells of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) to their normal cellular counterparts and found the basic leucine zipper protein ATF-like 3 (BA...

Classical Hodgkin lymphoma (cHL) is a hematopoietic malignancy with a characteristic cellular composition. The tumor mass is made up of infiltrated lymphocytes and other cells of hematologic origin but only very few neoplastic cells that are mainly identified by the diagnostic marker CD30. While most patients with early stage cHL can be cured by st...

The hallmark of classical Hodgkin lymphoma (cHL) is the presence of giant, mostly multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Whereas it has recently been shown that giant HRS cells evolve from small Hodgkin cells by incomplete cytokinesis and re-fusion of tethered sister cells, it remains unsolved why this phenomenon particularly takes plac...

Quantification of immunofluorescence stainings for LDHB, SHFM1 and HSPA8 in small and big HRS cells of the cell lines L-428 and L-1236. Whereas a significant difference in mean fluorescence intensity between small Hodgkin and big RS cells of the L-1236 was observed with one antibody against HSPA8 (B, GeneTex antibody, p<0.05, t-test), this was not...

DP L-428 cells separated by size-exclusion. L-428 cells were placed onto a 50 μm cell strainer. Cells smaller than 50 μm (small) passed the filter, whereas cells bigger than 50 μm (big) were retained. Subsequently, the separated populations were analyzed for CD15/CD30 expression. (A) Exemplary dot blots of small and big L-428 cells. Frequency of DP...

Big L-428 cells show the highest amount of DP cells. (A) L-428 cells were sorted by cell size (small, middle, big) or after staining for CD15 and CD30 into CD15+CD30+ DP and CD15-CD30+ SP cells. (B+C) Compared to the bulk population, populations sorted for cell size were analyzed for CD15 and CD30 expression by FACS. (B) Frequency of CD15-CD30+ SP...

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma, but can transform into diffuse large B cell lymphoma (DLBCL), showing a more aggressive clinical behavior. Little is known about these cases on the molecular level. Therefore, the aim of the present study was to characterize DLBCL transformed from NLPHL (LP-DLBCL) by g...

Growing attention in mature T-cell lymphomas/leukemias (MTCL) is committed to more accurate and meaningful classifications, improved pathogenetic concepts and expanded therapeutic options. This requires considerations of the immunologic concepts of T-cell homeostasis and the specifics of T-cell receptor (TCR) affinities and signaling. Scientists fr...

Hodgkin lymphoma (HL) presents with a unique histologic pattern. Pathognomonic Hodgkin and Reed-Sternberg (HRS) cells usually account for less than 1% of the tumor and are embedded in a reactive infiltrate mainly comprised of CD4+ T cells. HRS cells induce an immunosuppressive microenvironment and thereby escape anti-tumor immunity. To investigate...

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)—a subtype of Hodgkin lymphoma (HL)—is characterized by a low content of tumor cells, the LP cells. Transformation into diffuse large B cell lymphoma (DLBCL) occurs in about 10% of patients. We performed whole genome mutation analysis of the DLBCL components from two composite lymphomas consist...

Multinucleated giant tumor cells are frequently observed in tissue sections of lymphoma patients. In Hodgkin lymphoma (HL), these cells are pathognomonic for the disease and named Reed-Sternberg (RS) cells. Despite the well-described disease-promoting functions of RS cells, their development has remained obscure. We addressed this open question by...

Question: In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T cell/histiocyte rich large B cell lymphoma (THRLBCL) is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants...

The multinucleated Reed-Sternberg (RS) cells are pathognomonic for classical Hodgkin lymphoma (HL) and their presence is essential for diagnosis. However, the development of these giant tumor cells is controversially discussed. It was postulated that RS cells arise from mononucleated Hodgkin cells via endomitosis. Conversely, continuous single cell...

Cannabinoid receptor 1 (CB1) is expressed in certain types of malignancies. An analysis of CB1 expression and function in Hodgkin lymphoma (HL), one of the most frequent lymphomas, was not performed to date. We examined the distribution of CB1 protein in primary cases of HL. Using lymphoma derived cell lines, the role of CB1 signaling on cell survi...

Significance Multinucleated giant tumor cells are frequently observed in tissue sections of patients with cancer. In classical Hodgkin lymphoma (HL), these so-called Reed–Sternberg (RS) cells are pathognomonic for the disease. Despite the well-described disease-promoting functions of multinucleated RS cells, their development remains obscure. Long-...

In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T cell/histiocyte rich large B cell lymphoma (THRLBCL) is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL w...

Retroviral vectors (RVs) are powerful tools in clinical gene therapy. However, stable genomic integration of RVs can be oncogenic, as reported in several animal models and in clinical trials. Previously, we observed that T-cell receptor (TCR) polyclonal mature T cells are resistant to transformation after gammaretroviral transfer of (proto-)oncogen...

Combination antiretroviral therapy is highly effective in HIV infection, leading to decreased incidences of AIDS-defining neoplasms. However, HIV patients still have a 10-fold increased risk of developing classical Hodgkin lymphoma compared with the general population. As Hodgkin- and Reed-Sternberg cells represent only a minority in the tumor infi...

Mature T-cell lymphomas (MTCL) have an extremely poor prognosis and are much less frequent than immature T-cell leukemias. This suggests that malignant outgrowth of mature T lymphocytes is well controlled. Indeed, in a previous study we found that mature T cells are resistant to transformation with known T-cell oncogenes. Here, however, we observed...

The productive replication of human immunodeficiency virus type 1 (HIV-1) occurs exclusively in defined cells of human or chimpanzee origin, explaining why heterologous animal models for HIV replication, pathogenesis, vaccination, and therapy are not available. This lack of an animal model for HIV-1 studies prompted us to examine the susceptibility...