We propose a potential model for targeting GSCs in heterogeneous tumors, whereby differentiated GBM cells infected with G207-NKG2D BiTE produce NKG2D BiTE locally, directing T-cell cytotoxicity towards the GSC subpopulations in the tumor microenvironment.

P1, N=14, Completed, BioSyngen Pte Ltd | Trial completion date: Jan 2028 --> Apr 2024 | Trial primary completion date: Jan 2028 --> Apr 2024 | Not yet recruiting --> Completed

These studies show that the multispecific-targeting strategy used with MP0533 holds promise for improved selectivity towards LSCs and efficacy against clonal heterogeneity, potentially bringing a new therapeutic option to this group of patients with high unmet need. MP0533 is currently being evaluated in a dose-escalation phase 1 study in patients with relapsed or refractory AML (NCT05673057).

Here, we develop a smart DNA-based nanodrug, termed Endo-rDFN, by precisely assembling the antiangiogenic agent, endostar (Endo), into a reconfigurable DNA framework nanotube (rDFN) that could recognize tumor-overexpressed nucleolin to achieve the targeted delivery and controllable release of Endo. Endo-rDFN can not only effectively enhance the tumor-targeting capability of Endo and maintain its efficient accumulation in tumor tissues but also achieve on-demand release of Endo at tumor sites via the specific DNA aptamer for tumor-overexpressed nucleolin, named AS1411. We also found that Endo-rDFN exhibited significant inhibition of angiogenesis and tumor growth, while also providing effective protection against multiorgan injury (heart, liver, spleen, kidney, lung, etc.) to some extent, without compromising the function of these organs. Our study demonstrates that rDFN represents a promising vector for reducing antiangiogenic therapy-induced multiorgan injury, highlighting its potential for promoting the clinical application of antiangiogenic agents.

Clinical Trial Registration Number: NCT05199272

P1, N=0, Withdrawn, Weill Medical College of Cornell University | N=30 --> 0 | Initiation date: Jun 2023 --> Nov 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: Aug 2024 --> Dec 2025

P1, N=12, Recruiting, Peking University

P3, N=214, Recruiting, Philogen S.p.A. | Trial primary completion date: Dec 2023 --> Oct 2024

This study provides important insights into how the use of active drug PK assays, coupled with mechanistic follow-up, can inform and enable ongoing benefit/risk assessment for individuals participating in FIH dose-escalation trials. Translational studies that lead to a better understanding of the underlying biology of cognate T- and B-cell interactions, ultimately resulting in ADA development to novel biotherapeutics, are needed.

TALL-104 and NK-92MI-mediated cell killing assays were used to examine the immune resistance of UM cells...Notably, lactate secreted by IL-6-treated UM cells was crucial in influencing PD-L1 and HLA-E stability via the GPR81-cAMP-PKA signaling pathway. Our data reveal a novel mechanism by which UM cells acquire an immune-escape phenotype by metabolic reprogramming and reinforce the importance of the link between inflammation and immune escape.

We demonstrated that DLL3 trispecific induced better tumor growth control and a marked increase in the number of intratumoral T cells compared with a conventional DLL3-targeted bispecific T-cell engager. These findings suggest that DLL3 trispecific can exert potent efficacy by inducing concurrent CD137 costimulation and provide a promising therapeutic option for SCLC.

P1/2, N=141, Active, not recruiting, 23andMe, Inc. | Recruiting --> Active, not recruiting

We demonstrated that DLL3 trispecific induced better tumor growth control and a marked increase in the number of intratumoral T cells compared to a conventional DLL3-targeted bispecific T-cell engager. These findings suggest that DLL3 trispecific can exert potent efficacy by inducing concurrent CD137 costimulation and provide a promising therapeutic option for SCLC.

P1, N=15, Recruiting, Eutilex | Not yet recruiting --> Recruiting | Trial completion date: May 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Apr 2025

P1, N=180, Recruiting, Numab Therapeutics AG

P1/2, N=36, Active, not recruiting, TCR2 Therapeutics | Recruiting --> Active, not recruiting | N=175 --> 36 | Trial completion date: Apr 2026 --> Nov 2028 | Trial primary completion date: Jul 2024 --> Nov 2028

P1/2, N=6, Active, not recruiting, TCR2 Therapeutics | Trial completion date: Dec 2027 --> Oct 2028 | Trial primary completion date: Nov 2023 --> Oct 2028

P2, N=162, Active, not recruiting, Philogen S.p.A.

P1, N=60, Active, not recruiting, NeoTX Therapeutics Ltd. | Phase classification: P1b --> P1 | Trial completion date: Aug 2025 --> Oct 2026 | Trial primary completion date: May 2025 --> Oct 2026

P2, N=38, Completed, NeoTX Therapeutics Ltd. | Active, not recruiting --> Completed | Phase classification: P2a --> P2 | Trial completion date: Jul 2024 --> Jan 2024

P1; Trial completion date: Jan 2023 --> May 2024

P1, N=44, Terminated, Sanofi | N=200 --> 44 | Trial completion date: Feb 2026 --> Jan 2024 | Recruiting --> Terminated | Trial primary completion date: Feb 2026 --> Jan 2024; Sponsor's decision. Termination decision unrelated to safety profile

P1, N=8, Active, not recruiting, City of Hope Medical Center | Phase classification: P1b --> P1 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

Moreover, ALKBH6V83M and GAAI823T peptides from PC-B-148CA remarkably stimulated IFN-γ- and CD107a-positive T cells, displaying high cell-killing activity against target cancer cells. In summary, our findings underscore the successful identification of neoantigens with anti-tumor T cell functions and highlight the potential of personalized neoantigens as a promising avenue for breast cancer treatment.

Both cannabinoid-treated cultures had a smaller population of the calcium-positive population as compared to vehicle-treated cells. These results demonstrate the establishment of an in vitro model that can be used to mimic MOG-reactive T cell stimulation in vivo.

P1/2, N=110, Active, not recruiting, Triumvira Immunologics, Inc. | Recruiting --> Active, not recruiting

P1/2, N=33, Completed, Craig L Slingluff, Jr | Recruiting --> Completed

P1/2, N=111, Recruiting, Georgiamune Inc | Not yet recruiting --> Recruiting

See related article by Nolan-Stevaux et al., p. 90 (7). See related article by Kelly et al., p. 76 (8).

P1, N=345, Recruiting, Nurix Therapeutics, Inc. | Phase classification: P1b --> P1 | Trial completion date: Feb 2025 --> Feb 2026

After the initial induction chemotherapy, her disease remained refractory, and the patient received salvage immunotherapy with blinatumomab and inotuzumab ozogamicin. We present this case to highlight the potential of KMT2A-rearranged B-ALL to undergo lineage switch following B-cell targeted therapy. Patients with this kind of B-ALL should therefore be closely monitored to capture potential changes in the nature of the disease and prompt appropriate treatment.

Multiple vaccination formulations, including synthetic long peptides and viruses, empower CD3 bsAb therapy. Our results imply that eliciting tumor infiltration with vaccine-induced tumor-(un)related T cells can greatly improve the efficacy of CD3 bsAbs in solid tumors.

BsAbs have the potential to change the treatment paradigm of lymphoid malignancies in the coming years; however, longer follow-ups are required to assess the durability of responses to these agents. We herein provide an overview of the findings of recent clinical trials on BsAbs, including mechanisms of action, safety profiles, and efficacy, and discuss the role of BsAbs in the treatment of B-cell lymphomas and multiple myeloma.

P1, N=19, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2023 --> Dec 2024

P1, N=100, Recruiting, Imugene Limited

P1, N=21, Active, not recruiting, University of Florida

P1, N=150, Recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P1/2, N=240, Recruiting, Sanofi | Trial completion date: Jun 2027 --> Mar 2028 | Trial primary completion date: Apr 2027 --> Jan 2027

P1/2, N=6, Active, not recruiting, TCR2 Therapeutics | Recruiting --> Active, not recruiting | N=140 --> 6 | Trial primary completion date: Jun 2025 --> Nov 2023

HPN328 is well tolerated and clinically active. MTD determination, dose escalation, and dose optimization are ongoing. Updated safety and efficacy results including recently enrolled NEPC and SCBC pts will be presented.

T cells expressing a mesothelin (MSLN)-specific T cell receptor fusion construct (TRuC), called TC-210, have demonstrated robust antitumor activity in preclinical models of mesothelioma, ovarian cancer, and lung cancer. These data demonstrate that integration of a PD1-CD28 CSR into TRuC-T cells improves effector function, resistance to exhaustion, and prolongs persistence. Based on these findings, TC-510 is currently being evaluated in patients with MSLN-expressing solid tumors.

No grade ≥3 treatment-related AEs occurred in ≥10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in locally advanced/metastatic urothelial carcinoma.