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Tmod CAR T-Cell Therapy Offers Precise Targeting of Solid Tumors

The BASECAMP-1 study is identifying patients with human leukocyte antigen (HLA) loss of heterozygosity (LOH) for future use of these therapies.

A2 Biotherapeutics has announced positive preclinical feasibility data on their mesothelin (MSLN) and carcinoembryonic antigen (CEA)-targeted Tmod chimeric antigen receptor (CAR) T-cell therapies, as well as data from their observational BASECAMP-1 study (NCT04981119).1

These data were presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), November 10-14, 2021.

“We are pleased... to present updates on our progress advancing the novel Tmod™ platform for the treatment of solid tumors, including supporting pre-clinical evidence for CEA (A2B530) and MSLN (A2B694) and an overview of our observational study BASECAMP-1 to identify patients that may benefit from future Tmod™ CAR T cell therapy,” said Scott Foraker, JD, president and chief executive officer, A2 Bio, in a statement.1 “Our Tmod™ platform is a truly novel approach that has the potential to transform cancer treatment where current treatment approaches fall short, and we are working diligently to demonstrate this.”

Data on the Tmod technology were presented by Agnes Hamburger, PhD, vice president, drug discovery, A2 Biotherapeutics.2 Hamburger presented data that showed that the Tmod system has a robust protective effect on surrogate normal human cells in vitro, even in mixed-cell populations, while also yielding a robust cytotoxic effect on tumor cells in xenograft models. The system, which targets MSLN and CEA, can be paired with other blockers to scale the approach beyond HLA-A*02 patients.

Hamburger concluded that “the Tmod mechanism may provide an alternative route to leverage solid-tumor antigens such as MSLN and CEA in safer, more effective ways than previously possible.”

Data from the BASECAMP-1 study were presented by Julian Molina, MD, PhD, professor, oncology, Mayo Clinic.3 Molina discussed the advantages of Tmod technology and how the dual receptors in the engineered therapies tackle challenges of traditional cell therapies in solid tumors.

BASECAMP-1 is identifying patients with relapsed solid tumors with human leukocyte antigen (HLA) loss of heterozygosity (LOH) as a future target for Tmod cell therapies. The targets, which are present in around 13% across all solid tumors and up to 33% of pancreatic cancers, represent a promising target for cell therapies. The study is also assessing leukapheresis and manufacturing feasibility for future Tmod therapies.

During the study, participants will be screened with central next-generation sequencing to identify germline HLA-A*02 heterozygosity. If confirmed, then xT-Onco NGS testing will determine if somatic tumor HLA-A*02 LOH is present in primary archival tumor tissue. If a participant passes all screenings, they will undergo leukapheresis, be monitored for safety after leukapheresis, and followed for relapses. If relapse occurs, the participant’s banked T cells will be available for autologous CAR T-cell therapy.

“BASECAMP-1 is a premier example of precision medicine. The goal is to identify incurable metastatic, unresectable locally advanced solid tumor patients that may benefit from future Tmod™ CAR T cell therapy. The pre-clinical Tmod™ CAR T cell therapy data is promising and we hope to translate this technology from bench to bedside to offer patients a potential treatment for solid tumors,” Molina added.1

For more coverage of SITC 2021, click here.

REFERENCES
1. A2 Bio to Highlight Program Updates in Two Presentations at SITC 2021. News release. A2 Bio Therapeutics. November 1, 2021. https://www.businesswire.com/news/home/20211101005077/en/A2-Bio-to-Highlight-Program-Updates-in-Two-Presentations-at-SITC-2021
2. Hamburger A, Xu H, Ando Y, et al. A powerful, precise targeting system controlled by tumor deletions transforms CEA and MSLN CAR-T cells into tumor-selective agents. Presented at: 2021 SITC Annual Meeting; November 10-14, 2021; Washington, DC. Abstract 122.
3. Molina J, Go W, Kopetz S, et al. BASECAMP-1: an observational study to identify relapsed solid tumor patients with human leukocyte antigen (HLA) loss of heterozygosity (LOH) and leukapheresis for future CAR T-cell therapy. Presented at: 2021 SITC Annual Meeting; November 10-14, 2021; Washington, DC. Abstract 491.