P=N/A, N=11, Recruiting, Stiftung Swiss Tumor Institute | Trial completion date: Apr 2023 --> Apr 2025 | Trial primary completion date: Apr 2023 --> Apr 2025

P1, N=24, Recruiting, Sonoma Biotherapeutics, Inc.

P1, N=39, Recruiting, Kite, A Gilead Company | Trial primary completion date: Mar 2025 --> Dec 2027

P1/2, N=96, Recruiting, Multitude Therapeutics Inc. | Not yet recruiting --> Recruiting

P1, N=41, Recruiting, Cartesian Therapeutics

These findings confirm that autophagy signaling in B-cell malignancies is essential for the effective cytotoxic function of CAR-T cells and thereby pave the way for the development of autophagy-targeting strategies to improve the clinical efficacy of CAR-T cell immunotherapy.

P1/2, N=96, Not yet recruiting, Multitude Therapeutics Inc.

P1, N=24, Recruiting, Sonoma Biotherapeutics, Inc.

P1/2, N=22, Active, not recruiting, Sangamo Therapeutics | Recruiting --> Active, not recruiting | N=42 --> 22

P1/2, N=33, Recruiting, Quell Therapeutics Limited | Trial completion date: Mar 2039 --> Mar 2040 | Trial primary completion date: Jun 2025 --> Sep 2025

P1, N=39, Recruiting, Kite, A Gilead Company

P1, N=12, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial primary completion date: Oct 2023 --> Dec 2024

AMT-253, an MUC18-directed ADC based on topoisomerase I inhibitor exatecan and a self-immolative T moiety, had a higher therapeutic index compared with its microtubule inhibitor-based counterpart and favorable pharmacokinetics and tolerability in monkeys...Beyond melanoma, AMT-253 was also efficacious in a wide range of MUC18-expressing solid tumors. Efficient target/antibody discovery in combination with the T moiety-exatecan linker-payload exemplified here may facilitate discovery of new ADC to improve cancer treatment.

P1, N=54, Recruiting, Multitude Therapeutics (Australia) Pty Ltd | Not yet recruiting --> Recruiting

P1, N=39, Recruiting, Kite, A Gilead Company | Not yet recruiting --> Recruiting

Methods and Through short-term killing assays, we compared CART19 alone to CART19 combined with the EZH2 inhibitor tazemetostat (taz), and demonstrated that taz enhances CART19 tumor killing of DLBCL cell lines [OCI-Ly18 and Toledo (with wild-type EZH2) and SU-DHL-4 (with mutant EZH2)]...We retrospectively analyzed a cohort of large B-cell lymphoma patients treated with commercial CART19 (tisagenlecleucel and axicabtagene ciloleucel) at the University of Pennsylvania between January 2018 and March 2023 for response (Lugano criteria) according to their EZH2 mutational status... Our data demonstrate that modulation of EZH2 enhances CART19 immunotherapy in preclinical models of lymphoma. EZH2 inhibition rewires lymphoma immunogenicity, making tumor cells more susceptible to CART19 killing and reducing CART19 terminal differentiation. By understanding and modulating the interplay between tumor and CART cells, we can unlock the full potential of CART19 immunotherapy in DLBCL/FL patients, aiming at long-lasting treatment outcomes.

Taken together, these data suggest that intravenous delivery of INT2104 will be both safe and effective, providing a faster, cheaper, and more accessible option for treatment of B cell malignancies. Ongoing efforts include a GLP Toxicology study to enable IND submission in 2Q2024.

P1, N=14, Recruiting, The Affiliated Hospital of Xuzhou Medical University

P1, N=39, Not yet recruiting, Kite, A Gilead Company

Conclusions AB-1015 is specific for ALPG/P+MSLN+, demonstrates superior potency compared with logic gated T cells alone, and is resistant to ovarian TME suppression in preclinical studies. Based on these promising preclinical data, AB-1015 is being studied in a phase I clinical trial (NCT05617755).

The interim results of this phase 1 study support further investigation of base-edited T cells for patients with relapsed leukemia and indicate the anticipated risks of immunotherapy-related complications. (Funded by the Medical Research Council and others; ISRCTN number, ISRCTN15323014.).

P1, N=10, Recruiting, Great Ormond Street Hospital for Children NHS Foundation Trust | Not yet recruiting --> Recruiting

P1, N=10, Not yet recruiting, Great Ormond Street Hospital for Children NHS Foundation Trust

P1, N=10, Recruiting, Great Ormond Street Hospital for Children NHS Foundation Trust | Trial completion date: Sep 2024 --> Feb 2025

Moreover, the self-delivery of TIGIT-blocking scFvs enhanced the infiltration and activation of MT CAR-T cells in the tumor microenvironments to achieve better tumor regression in vivo. These results suggest that blocking TIGIT effectively enhances the anti-tumor effect of CAR-T cells and suggest a promising strategy of combining CAR-T with immune checkpoints blockade in the treatment of solid tumors.

P1, N=54, Not yet recruiting, Multitude Therapeutics (Australia) Pty Ltd

Combination therapy of FAP UCAR, Meso UCAR T cells and the checkpoint inhibitor anti-PD-1 significantly reduced tumor burden and prolonged mice survival. Our study thus proposes a novel treatment paradigm for successful CAR T-cell immunotherapy against stroma-rich solid tumors.

P1, N=16, Recruiting, Shanghai Simnova Biotechnology Co.,Ltd.

BCMA-targeting modular P329G-CAR-T cell therapy IBI346 was well tolerated and showed preliminary clinical activity in heavily pretreated pts with RRMM. To realize the full potential of this modular CAR-T cell product, the dose and regimen of the P329G antibody and CAR-T cells requires further exploration. Correspondence to Dr.

Thus, we concentrate on the biomarkers that can predict responses and outcomes after CD19-directed CAR-T immunotherapy. Furthermore, the mechanisms that may lead to treatment failure are also discussed in this review.

As a result, AB-1015 is capable of completely clearing these otherwise difficult-to-treat tumors in this model.In summary, AB-1015 is specific for ALPG/P+MSLN+, demonstrates superior potency, expansion, and persistence compared with logic gated T cells alone, and is resistant to ovarian TME suppression in preclinical studies. Based on these promising preclinical data, AB-1015 is being studied in a phase I clinical trial (NCT05617755) to assess the safety, pharmacokinetics, immunogenicity, and efficacy for patients with platinum-resistant ovarian cancer.

RVG modification enables CAR-T cells to cross the BBB, and stimulation with glioma cells induces 70R CAR-T cells to expand in a resting state. The modification of RVG29 has a positive impact on CAR-T therapy for brain tumors and may have potential in CAR-T therapy for glioma.

Using xenograft mice, we confirmed that CAR-T function could also be inhibited by MSC in vivo and STC1 played a critical role. These data revealed a novel function of MSC and staniocalcin-1 in suppressing CAR-T efficacy, which should be considered in cancer therapy and may also have potential applications in controlling the toxicity arising from the excessive immune response.

Taken together, our results suggest that CX804 exerts potent and specific effect against L1CAM positive cancer cells in vitro and in vivo. Furthermore, we propose that newly established CAR-T cells targeting L1CAM facilitate therapy against L1CAM-positive ovarian and gastric cancer patients

PHGDH inhibition activates anti-tumor T cell immunity and sensitizes GBM to CAR T therapy. Thus, reprogramming endothelial metabolism by targeting PHGDH may offer a unique opportunity to improve T cell-based immunotherapy.

Furthermore, GA may directly target and activate STAT3, which may, at least in part, contribute to STAT3 activation. Overall, the findings reported here suggested that the combination of anti-CD19 CAR-T immunotherapy with GA would be a promising approach to increase the anti-lymphoma efficacy.

P1, N=7, Recruiting, Beijing Boren Hospital | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2022 --> Dec 2024

Both CD22 and CD19/CD22 CAR-T immunotherapy demonstrated favorable efficacy and acceptable adverse events in the treatment of hematologic malignancies. Well-designed and large sample-sized clinical trials are warranted.

In the real-world optimal sequencing of available standard treatment remains a challenge in patients refractory to CAR T-cell therapy. Clinical trials evaluating novel treatments and publications of institutional case series could help expand access to treatments that may be beneficial for CAR-T refractory patients.

In this work we performed phenotypic and functional characterization of CAR-T generated from healthy donors and MM patients at different disease stage.Method ology: Second generation CAR-T cells targeting BCMA and co-expressing BFP as a reporter gene (modified from ARI0002h CAR-T sequence1), were generated by lentiviral transduction of aCD3/aCD28 activated T cells, from each group of donor/patients, and expanded in the presence of IL-7/IL-15...Conclusion s : Our results would indicate that CAR-T generated from patients at later stages of the disease present a more differentiated phenotype, with reduced functionality and increased exhaustion features, that could compromise antitumor efficacy. Transcriptomic analysis allows the identification of molecular mechanisms that could be modulated for the development of improved therapies.

P1, N=60, Recruiting, Arsenal Biosciences, Inc. | Not yet recruiting --> Recruiting

P1, N=60, Not yet recruiting, Arsenal Biosciences, LLC