In TCL models with dependence on MCL-1, combining CAR-37 T cells and the MCL-1 inhibitor AZD5991 increases anti-TCL response and prolongs survival of xenografted mice. These findings suggest that personalized selection of BH3 mimetic/CAR-T combinations could maximize the therapeutic index for patients with TCL and possibly other diseases.

P1/2, N=191, Completed, Nordic Nanovector | Active, not recruiting --> Completed

P1, N=7, Completed, Nordic Nanovector | Phase classification: P1b --> P1

P1/2, N=46, Terminated, Genmab | N=182 --> 46 | Trial completion date: Sep 2025 --> Jul 2023 | Recruiting --> Terminated | Trial primary completion date: Sep 2023 --> Nov 2022; Due to strategic evaluation of GEN3009 within context of Genmab's portfolio, decision not based on any safety or regulatory concerns.

P1/2, N=182, Recruiting, Genmab | Trial completion date: Apr 2025 --> Sep 2025 | Trial primary completion date: Dec 2023 --> Sep 2023

P1a/1b, N=110, Recruiting, Qilu Puget Sound Biotherapeutics (dba Sound Biologics) | Not yet recruiting --> Recruiting

P1/2, N=182, Recruiting, Genmab | N=120 --> 182 | Trial completion date: May 2023 --> Apr 2025 | Trial primary completion date: Nov 2022 --> Dec 2023

P1a/1b, N=110, Not yet recruiting, Qilu Puget Sound Biotherapeutics (dba Sound Biologics)

Besides, some patients relapsed after anti-CD19 CAR-T cell therapy, which possibly were due to limited CAR-T cells persistence, CD19 antigen escape or antigen down-regulation. Quite a few new antigen-targeted CAR-T products and new-generation CAR-T, for example, CD20-targeted CAR-T, CD79b-targeted CAR-T, CD37-targeted CAR-T, multi-antigen-targeted CAR-T, armored CAR-T and four-generation CAR-T are developing rapidly to figure out these deficiencies.

RASGRP2 was abnormally expressed in lung adenocarcinoma and correlated with the infiltration level of immune related cells, which might influence the efficacy of immunotherapy.

In the absence of myeloma cells, lenalidomide and pomalidomide induce CD4 T cell secretion of IL-2 and indirect activation of Natural Killer (NK) cells...Furthermore, combination treatment of IMiDs and myeloma-targeting monoclonal antibodies eg. daratumumab (anti-CD38) and elotuzumab (anti-SLAMF7), checkpoint inhibitors, or bispecific T cell engagers showed synergistic effects, mainly via enhanced T and NK cell dependent cellular toxicity and T cell proliferation. Conversely, the corticosteroid dexamethasone can impair the immune modulatory effects of IMiDs, indicating that careful choice of myeloma drugs in combination with IMiDs is key for the best anti-myeloma therapeutic efficacy. This review presents an overview of the role for T cells in the overall anti-myeloma effects of immunomodulatory drugs.

The bi-specific hCD37-CD19 significantly inhibited Raji xenograft tumor growth and prolonged mouse survival in NOD scid gamma mouse (NSG) mouse model. This study demonstrates that novel humanized CD37 and humanized CD37-CD19 CAR-T cells specifically targeted either CD37 positive or CD37 and CD19-positive cells and provides a basis for future clinical studies.