ADI-270: an armored allogeneic gamma delta T cell therapy designed to target CD70-expressing solid and hematologic...

Area of Science:

• Immunology
• Oncology
• Cell Therapy

Background:

• Conventional CAR-T cell therapy faces challenges in the tumor microenvironment (TME), including immunosuppression and antigen heterogeneity.
• Gamma delta (γδ) T cells offer potential advantages due to their innate/adaptive immunity and tissue tropism.
• ADI-270 is an allogeneic γδ CAR-T cell therapy targeting CD70+ cancers, engineered for enhanced efficacy.

Purpose of the Study:

• To preclinically characterize ADI-270, a novel γδ CAR-T cell therapy.
• To evaluate ADI-270's efficacy and safety against CD70+ cancers.
• To assess ADI-270's ability to overcome tumor microenvironment-mediated resistance.

Main Methods:

• Vδ1 T cells were engineered with an anti-CD70 CAR and dominant-negative TGFβ receptor II (dnTGFβRII).
• Phenotype and function were assessed using in vitro cell culture and in vivo xenograft models.
• ADI-270 was evaluated for cytotoxicity, cytokine profile, TGFβ resilience, alloreactivity, and tumor control.

Main Results:

• ADI-270 showed potent in vitro cytotoxicity against diverse cancer cell lines, including those with low CD70 expression.
• The therapy demonstrated resilience to TGFβ inhibition and reduced alloreactive killing.
• ADI-270 exhibited robust tumor tropism and controlled tumor growth in preclinical models.

Conclusions:

• ADI-270 exhibits potent anti-tumor activity and overcomes TME limitations for CD70+ cancers.
• Functional armoring enhances efficacy and persistence within the TME.
• ADI-270 is advancing to clinical trials for relapsed/refractory clear cell renal cell carcinoma.