Session: 704. Immunotherapies: Poster III
Hematology Disease Topics & Pathways:
Biological, Diseases, Lymphoma (any), Therapies, CAR-Ts, Hodgkin Lymphoma, DLBCL, T-Cell Lymphoma, immunotherapy, Lymphoid Malignancies, Clinically relevant
Here we show that CD30.CAR-EBVSTs resist fratricide by masking their own CD30 molecules expressed in cis, but are nonetheless protected from rejection when co-cultured with alloreactive T cells expressing CD30 in trans. Notably, CD30.CAR EBVSTs preserve the function of both their TCR and the CD30.CAR, with retention of EBV specificity and the ability to eliminate CD30-positive tumor cells. We have manufactured a bank of clinical grade CD30.CAR EBVSTs from donors with HLA types designed to provide a partial HLA match for our diverse recipients. Clinical grade CD30.CAR EBVST cultures readily expanded to sufficient numbers for a planned clinical trial and expressed the CD30.CAR on 77% to 99% of cells. All of the lines passed functional release criteria of having greater than 100 IFNɣ spot-forming units (SFU) per 105 cells in response to both latent and lytic EBV antigens, and greater than 20% specific cytolysis against a CD30-positive Hodgkin lymphoma cell line, HDLM2, at an effector to target ratio of 20:1. Although CD30.CAR killing is not HLA restricted, we will select the CD30.CAR EBVST product for each recipient, based on the best HLA class I and class II match. This will allow endogenous EBV to boost the in vivo activity of CD30.CAR EBVSTs, and will provide additional reactivity for patients with CD30-positive and EBV-positive tumors. The IND for the clinical trial (NCT04288726) has been approved and we will recruit patients with CD30-positive lymphomas including Hodgkin lymphoma, diffuse large B cell lymphoma and NK/T cell lymphoma. In summary, we present an approach to making an off-the-shelf T cell therapy that can rapidly translate to the clinic, requires no gene editing, and can serve as a platform for other CAR/TCRs to target a multiplicity of malignancies.
Disclosures: Quach: Tessa Therapeutics: Research Funding. Brenner: Memmgen: Membership on an entity's Board of Directors or advisory committees; Allogene: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Walking Fish: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Maker Therapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Other: Founder; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Founder; Tumstone: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees. Heslop: Tessa Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Gilead Biosciences: Consultancy; PACT Pharma: Consultancy; Kiadis: Consultancy; AlloVir: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Marker Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Ramos: Novartis: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Kuur Therapeutics: Research Funding. Rouce: Novartis: Honoraria; Tessa Therapeutics: Other, Research Funding. Rooney: Marker Therapeutics: Current equity holder in publicly-traded company, Other: co-founder; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Allovir: Current equity holder in publicly-traded company, Other: co-founder.