Adoptive Immune Responses to Sars-Cov2 Vaccination in CART19 Treated Patients

ABSTRACT

Background: The two FDA approved mRNA-based SARS-CoV2 vaccines have shown >90% efficacy at preventing COVID and eliciting protective immunity in nearly all healthy individuals. However, the extent of vaccine induced antibody and T cell immunity in immunocompromised patients is not well known. Our study objective is to determine if patients with hematologic malignancies treated with B-cell targeting chimeric antigen receptor (CAR) T cell therapies can mount antibody and T cell immune responses to SARS-CoV2 vaccines. A prospective single-center study to evaluate the SARS-CoV2 immune responses in immunocompromised individuals (COVAX Study) was initiated at University of Pennsylvania following the IRB guidelines. The study enrolled 8 healthy adults,12 patients are in remission after treatment (average of 40.6 months) with CART cells targeting either CD19 or CD19+CD22 and received both doses of SARS-CoV2 vaccine. Methods and Results: Serology to SARS-CoV2 spike-receptor binding domain (RBD) IgG, RBD-IgA, RBD-IgM and spike-specific T cell responses were measured prior to vaccination and serially up to 28 days after booster vaccination. RBD-IgG and RBD-IgA were detected in 8/8 and 7/8 healthy subjects compared to 5/12 and 2/12 CART patients, respectively (Figure A). In the CART cohort, several patients who demonstrated an induction of RBD-IgG (57.2/uL +/- 20.2) compared to those who were RBD-IgG-negative (9/uL +/- 10.1, ANOVA with multiple comparisons test p=0.017) have higher level of circulating B cells. No association was found with time since CART infusion, age, disease type, or vaccine manufacturer. All 8 healthy subjects demonstrated induction of SARS-Cov2 spike-specific CD4 + T cell immunity compared to 7 out of 11 CART patients (Figure B). RBD-IgG responses were not correlated with CD4 + T cell activation (Pearson correlation, R=0.21, p=0.53). Indeed, 3 CART patients demonstrated robust CD4 + T cell activation despite absence of antibody induction. Overall, 8/12 CART patients demonstrated induction of either or both humoral and T cell immune responses. Conclusions: We show that immune responses to SARS-CoV2 mRNA vaccines are induced in majority of patients who have been treated with CART therapies targeting B-cell lineage antigens. Induction of vaccine-specific antibody was strongly associated with the level of circulating B cells. However, in CART cohort patients despite severe humoral immune deficiency, strong CD4 + T cell responses were observed suggestive of a sufficient protective immunity. [Formula presented] Disclosures Frey Novartis Research Funding;Sana Biotechnology Consultancy;Kite Pharma Consultancy;Syndax Pharmaceuticals Consultancy. Garfall Amgen Honoraria;CRISPR Therapeutics Research Funding;GlaxoSmithKline Honoraria;Janssen Honoraria, Research Funding;Novartis Research Funding;Tmunity Research Funding. Porter American Society for Transplantation and Cellular Therapy Honoraria;Genentech Current equity holder in publicly-traded company, Ended employment in the past 24 months;ASH Membership on an entity's Board of Directors or advisory committees;DeCart Membership on an entity's Board of Directors or advisory committees;Incyte Membership on an entity's Board of Directors or advisory committees;Janssen Membership on an entity's Board of Directors or advisory committees;Kite/Gilead Membership on an entity's Board of Directors or advisory committees;National Marrow Donor Program Membership on an entity's Board of Directors or advisory committees;Novartis Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding;Tmunity Patents & Royalties;Wiley and Sons Publishing Honoraria. June AC Immune, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm Consultancy;Tmunity, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm Current equity holder in publicly-traded company;Novartis Patents & Royalties.