Overcoming Challenges With CAR T Therapies in Solid Tumors: Julian Molina, MD, PhD


The hematologist/oncologist from Mayo Clinic discussed the role of HLA loss in a variety of cancers.

“The problem has been when CAR T was tested and introduced to treat solid tumors, there was a lot of toxicity... from off-target effects... The 2 best examples are the mesothelin CAR T-cell and the CEA CAR T-cell studies that again resulted in significant off-target toxicity. So, 1 way to overcome this off-target toxicity is to look for other events that happen in the cancer cells. And some of those events are driven by the HLA loss that occurs in tumors... which is quite frequently seen in cancers."

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) at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), November 10-14, 2021.1

Data from the BASECAMP-1 study were presented by Julian Molina, MD, PhD, professor, oncology, Mayo Clinic.2 The study is identifying patients with relapsed solid tumors with human leukocyte antigen (HLA) loss of heterozygosity (LOH)--which are present in approximately 13% of all solid tumors and up to 33% of pancreatic cancers--as a future target for Tmod cell therapies.The study is also assessing leukapheresis and manufacturing feasibility for future Tmod therapies.

GeneTherapyLive spoke with Molina to learn more about the challenges of CAR T-cell therapies in treating solid tumors and how Tmod technology may overcome these. He also discussed the role of HLA LOH in a variety of cancers.

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. 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.
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