A2 Bio to Present Early A2B694 CAR T Data in HLA-A*02 LOH Solid Tumors at ASCO 2026

A2 Biotherapeutics (A2 Bio), a US-based clinical-stage immunotherapy company, will present early clinical and preclinical updates on its logic-gated chimeric antigen receptor (CAR) T-cell programs for solid tumors at the upcoming 2026 American Society of Clinical Oncology annual meeting to held May 29-June 2 in Chicago. The presentations will include an initial safety and efficacy poster for CAR T candidate A2B694 and a phase 1/2 trial-in-progress update for the EVEREST-2 trial, according to a company announcement.¹ The presentations focus on patients with advanced solid tumors selected for HLA-A*02 loss of heterozygosity (LOH), a biomarker-based strategy intended to widen the therapeutic window for cell therapy in solid malignancies.

How could logic-gated CAR T-cell therapies improve safety and efficacy in solid tumors?

In a company press release, A2 Bio said the meeting “highlight[s] progress” across 3 posters.¹ The most clinically relevant of these posters appears to be an initial safety and efficacy report for A2B694, a mesothelin-targeted CAR T therapy derived from the company’s Tmod platform. This poster will be presented by Julian R. Molina, MD, PhD, of the Mayo Clinic.¹ For oncologists, the update is notable because effective CAR T approaches in solid tumors have remained elusive despite major advances in hematologic cancers, in part because of on-target off-tumor toxicity, antigen heterogeneity, and an immunosuppressive tumor microenvironment.^2,3

The ASCO listing indicates that A2B694 is being studied in patients with advanced solid tumors with HLA-A*02 LOH.¹ Mesothelin is overexpressed in several epithelial malignancies, including mesothelioma, pancreatic cancer, ovarian cancer, and subsets of lung adenocarcinoma, making it an attractive but biologically challenging target because of low-level expression in normal tissues.² The company’s Tmod platform is designed around a NOT-gate concept in which activation against a tumor antigen is modulated by recognition of a separate HLA signal. The aim is to spare normal cells that retain the HLA allele while allowing killing of tumor cells that have lost it.^1,3

The A2B694 presentation may include first-in-human safety and activity data, but the company did not provide details on sample size, dose levels, objective responses, duration of response, cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, or other adverse events in its press release.¹ Those data points will be important in assessing whether the approach offers a clinically meaningful signal in a setting where many cellular immunotherapy programs have struggled to achieve durable responses in solid tumors.^2,3

What role does IL-12–enhanced CAR T-cell design play in overcoming solid tumor resistance?

A second ASCO presentation is a trial-in-progress poster for the phase 1/2 study, EVEREST-2, which evaluated a logic-gated CAR T therapy consisting of an armored, membrane-tethered interleukin-12 (IL-12) “booster” in patients with advanced solid tumors with HLA-A*02 LOH.¹ IL-12 has long been of interest in cancer immunotherapy because of its capacity to stimulate cytotoxic immune responses, but systemic administration has been limited by toxicity. Engineered local or cell-bound approaches are one strategy to mitigate that problem.⁴

The third presentation will address the “influence of onboard, tethered IL-12 on potency of the Tmod NOT gate and selectivity.”¹ That poster may help explain the translational rationale for EVEREST-2.

Clinically, the updates arrive as the field continues to seek effective strategies for solid tumors after the success of CD19- and B-cell maturation antigen-directed CAR T products in hematologic malignancies.³ Unlike blood cancers, solid tumors present barriers that include inefficient trafficking, physical stromal constraints, antigen escape, and the risk of damaging normal tissues that express target antigens at low levels.² Mesothelin-directed approaches, including antibody-drug conjugates, bispecifics, and cell therapies, remain under investigation, but no mesothelin-directed CAR T therapy has yet established a standard role in routine practice.²

References

1. A2 Biotherapeutics. A2 Biotherapeutics to highlight progress of CAR T-cell clinical programs in three poster presentations during the American Society of Clinical Oncology (ASCO) 2026 Annual Meeting. Published April 21, 2026. Accessed April 23, 2026. https://www.a2bio.com/a2-biotherapeutics-to-highlight-progress-of-car-t-cell-clinical-programs-in-three-poster-presentations-during-the-american-society-of-clinical-oncology-asco-2026-annual-meeting/
2. Hassan R, Ho M. Mesothelin targeted cancer immunotherapy. Eur J Cancer. 2008;44(1):46-53. doi: 10.1016/j.ejca.2007.08.028
3. June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science. 2018;359(6382):1361-1365. doi: 10.1126/science.aar6711
4. Pan WY, Lo CH, Chen CC, et al. Cancer immunotherapy using a membrane-bound interleukin-12 with B7-1 transmembrane and cytoplasmic domains. Mol. Ther. 2012;20(5):927-37. doi: 10.1038/mt.2012.10