NGS assay by Tempus is able to identify GI cancer patients with clonal Human Leukocyte Antigen Loss of Heterozygosity (HLA LOH) for future Tmod™ CAR T Therapy
AGOURA HILLS, Calif., Jan. 18, 2022 /PRNewswire/ -- A2 Biotherapeutics, Inc. ("A2 Bio") is a biotechnology company focused on the development of a first-in-class, logic-gated Tmod™ CAR T cell therapy platform to tackle the fundamental challenge in solid tumor treatment—the ability of cancer medicines to distinguish between tumor and normal cells. The Tmod system exploits irreversible genetic changes in cancer cells called loss of heterozygosity (LOH). A2 Bio will be presenting on Saturday, January 22nd at the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium taking place virtually and in-person on January 20–22, 2022, at the Moscone Center in San Francisco, CA.
A2 Bio in partnership with Tempus, a leader in artificial intelligence and precision medicine, analyzed the Tempus xT NGS assay database that has over 21,000 samples with HLA locus LOH data and over 10,000 of which are from patients with advanced disease stage ≥ 3; 3,000 of these samples are from GI cancer patients. These results demonstrate clonal frequency of HLA LOH in advanced GI solid tumor cancers of 16.3%, with a range of 15.6%-20.8% among colorectal, pancreatic, and gastroesophageal tumors. In addition, these frequencies are similar to primary tumors from The Cancer Genome Atlas (TCGA) database. Thus, HLA LOH is a well-defined discriminator between tumor and normal cells and can be exploited for NOT logic-gated Tmod™ CAR T to reduce on-target off-tumor toxicity. These results expand knowledge about HLA LOH in these tumors and pave the way for the use of Tempus xT NGS in screening patients for future Tmod™ CAR T cell therapy.
"A2 Bio has developed Tmod™ CAR T, which targets clonal HLA LOH as a clear differentiator between normal versus tumor cells," said William Go, MD, PhD, Chief Medical Officer at A2 Bio. "The Tempus xT next generation sequencing assay will be utilized in BASECAMP-1. BASECAMP-1 is a study to identify HLA LOH solid tumor cancer patients and obtain their T cells earlier in their treatment paradigm who may benefit from future carcinoembryonic antigen (CEA) and mesothelin (MSLN) Tmod™ CAR T therapy. Novel therapies are sorely needed in GI malignancies, especially in pancreatic cancer, where limited therapeutic advances have been made in over two decades."
Lead author J. Randolph Hecht, MD, Professor of Clinical Medicine, Director of the UCLA Gastrointestinal Oncology Program and principal investigator of the BASECAMP-1 trial, stated: "Tmod CAR T is an elegant and truly novel therapeutic utilizing a NOT logic gate to distinguish between normal and tumor cells. While other T cell therapies have failed in GI cancers due to toxicity or lack of efficacy, targeting HLA LOH with Tmod may provide the therapeutic safety window necessary for clinically significant outcomes. In addition, patients who might benefit from this approach can be identified using the widely used Tempus xT NGS assay early in the course of their disease."
ASCO GI Poster Information
Title: Next generation sequencing (NGS) to identify relapsed gastrointestinal (GI) solid tumor patients with human leukocyte antigen (HLA) loss of heterozygosity (LOH) for future logic-gated CAR T therapy to reduce on target off tumor toxicity
Presenter: J. Randolph Hecht, MD, Director of the UCLA Gastrointestinal Oncology Program
Session: Poster Session C: Cancers of the Colon, Rectum, and Anus.
Date/Time: Saturday, January 22 at 6:30 am to 7:55 am and 12:30 pm to 2:00 pm PT
Location: Abstract 190 - Level 1, West Hall; Moscone Center, San Francisco, CA
A2 Bio's posters presented can be viewed on the company's website at www.a2bio.com/science/abstracts-and-publications.
About A2 Biotherapeutics
A2 Biotherapeutics has invented the Tmod™ cell therapy platform to tackle the fundamental challenge in solid tumor treatment—the ability of cancer medicines to distinguish between tumor and normal cells. The Tmod™ mechanism utilizes two receptors to exploit common, specific gene losses in tumors which demarcate the tumor from normal cells. A2 is positioned to deliver a broad pipeline of both autologous and allogeneic cell products, with in-house cGMP manufacturing, a leadership team with 90+ years combined experience in biotech and cell therapy, and a world-class scientific advisory board. A2 is backed by investors that include The Column Group, Vida Ventures, Samsara BioCapital, Nextech Invest, Casdin Capital, Euclidean Capital, UC Investments (Office of the Chief Investment Officer of the Regents), Hartford HealthCare Endowment, StepStone Group, Schroders, Section 32 and Merck.
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SOURCE A2 Biotherapeutics