Gene therapy, cellular immunotherapy and vaccination - Biology & translational research

Reona Sakemura, Nan Yang, Michelle Cox, Sutapa Sinha, et al.

AXL-RTK INHIBITION DIRECTS THE FUNCTIONAL PHENOTYPE OF CHIMERIC ANTIGEN RECEPTOR T CELLS

Conclusion: We showed for the first time that Axl-RTK inhibition polarizes T cells into a Th1 functional phenotype, downregulates inhibitory receptors, and reduces myeloid associated cytokine production by CART19. The combination therapy yielded synergistic cytotoxicity against JeKo in vitro and in a CART19 relapse model. These findings encourage further study of Axl-RTK inhibition with TP-0903 as an enhancer of T cell immunotherapies.

Xiang-Yu Zhao, Qian Jiang, Hao Jiang, Li-Juan Hu, et al.

A NEW MEMBRANE-BOUND IL-21/4-1BBL-EXPANDED NK PRODUCT EXHIBITS ACTIVITY AGAINST ACUTE MYELOID LEUKEMIA ACTIVITY IN VIVO

Conclusion: In conclusion, this study demonstrated that mbIL-21/4-1BBL expanded NK cells exhibited anti-leukemia activity against AML in vitro and in a mouse model, and the infusion of expanded NK product was potentially efficacious for AML patient without adverse effects.

Afroditi Katsarou, Jort van der Schans, Renée Poels, Sonja Zweegman, et al.

A COMBINATORIAL RECEPTOR STRATEGY TO IMPROVE MULTIPLE MYELOMA THERAPY WITH CHIMERIC ANTIGEN RECEPTOR-ENGINEERED T LYMPHOCYTES

Conclusion:  In conclusion, we here show that double targeting MM with a BCMA-CAR and a CD38-CCR provides higher effector-MM avidity and full costimulation. Engagement of the CD38-CCR enhances the anti-MM cytotoxicity and persistence and reduces the exhaustion of double-targeting compared to conventional single-targeting CAR T cells. Therefore double-targeting of BCMA and CD38 is a powerful strategy to improve clinical outcomes of BCMA-CAR T cell therapy.

Gabriele Antonarelli, Adele Mucci, Giulia Escobar, Giacomo Desantis, et al.

LOCAL INTERFERON-ALPHA DELIVERY INTO THE MYELOMA MICROENVIRONMENT BY GENE-ENGINEERED AUTOLOGOUS STEM CELL TRANSPLANTATION

Conclusion: Our studies conducted both in the immunocompetent Vk*Myc murine model as well as in the hematochimeric xenotransplantation setting demonstrate that IFNa-GT has robust anti-MM effect and may subvert the immunosuppressive MM TME, acting both on myeloma cells as well as on the immune infiltrate. A phase I/II dose-escalation study of IFNa-GT in patients with early-relapsed multiple myeloma has recently been approved and is starting accrual in March 2019.  

POSTER PITCHES

Rogier Reijmers, Miranda Meeuwsen, Christiaan Kweekel, Michelle Kop, et al.

TRANSCRIPTION FACTOR BOB1 IS ESSENTIAL FOR GERMINAL CENTER-DERIVED B CELL MALIGNANCIES OFFERING AN ATTRACTIVE TARGET FOR TCR-BASED THERAPY

Conclusion: Altogether, we postulate BOB1 as an essential B cell lineage-specific target, fortifying gene transfer of our unique TCRs into CD8+ cytotoxic T cells as an efficient therapeutic treatment option for a large variety of B cell neoplasms.

Chrysoula Pantazi, Maria Alvanou, Kiriakos Koukoulias, Nikoletta Psatha, et al.

DEVELOPING A CRISPR-CAS9 TOOL TO INACTIVATE THE GLUCOCORTICOID RECEPTOR AND BROADEN THE APPLICABILITY OF ANTIGEN-SPECIFIC T-CELL IMMUNOTHERAPY

Conclusion: Overall, we provide a series of gRNAs to CRISPR/Cas9-disrupt the GR and confer resistance of T-cells to steroids. By this approach, we endeavor to ultimately offer the benefits of AI to the most vulnerable to infections patients, as those

Cassie Chou, Simon Paul Fräßle, Reed M. Hawkins, Rachel N. Steinmetz, et al.

EFFECTS OF NKTR-255, A POLYMER CONJUGATED HUMAN IL-15, ON EFFICACY OF CD19 CAR T CELL IMMUNOTHERAPY IN A PRECLINICAL LYMPHOMA MODEL.

Conclusion:  NKTR-255 administration improves the antitumor efficacy and kinetics of CD19 CAR T cells, supporting advancement into clinical trials of combination therapy with NKTR-255 and approved CD19 CAR T cell products.

Elena Maroto-Martín, Jessica Encinas, Almudena García-Ortiz, Rafael Alonso, et al. 

NKG2D AND BCMA-CAR NK CELLS EFFICIENTLY ELIMINATE MULTIPLE MYELOMA CELLS. A COMPREHENSIVE COMPARISON BETWEEN TWO CLINICALLY RELEVANT CARS.

Conclusion:  We have generated two novel and stable CAR NK-92 immunoproducts that improve the oncolytic efficacy of the parental cell line. Indeed, NKG2D-CAR NK-92MI cells are as equally efficient as BCMA-CAR NK-92MI cells to eradicate diverse MM cells. To summarize, all these data show the feasibility to use this NK ‘off-the-shelf’ approach as immunotherapy for MM.

Panagiota A Sotiropoulou, Alexandre Michaux, Susanna Raitano, Simon Bornschein, et al. 

DEVELOPMENT OF A NEXT GENERATION ALLOGENEIC CAR-T CELL PLATFORM WITHOUT GENE EDITING

Conclusion:  This work demonstrates that the expression of shRNA in a standard retroviral vector provides a one-step solution to produce cells suitable for Allogeneic CAR T cell therapy. Our testing continues, involving the examination of the anti-tumor potency of such shRNA-Allo CAR-T cells. Importantly, this approach provides a one vector solution that offers an alternative to strategies such as gene editing to eliminate the TCR, while also requiring no major alteration to current CAR-T cell manufacturing, that should enable the rapid adoption of the approach into clinical testing.