- BA01 Best abstracts & Awards
- BA02 Best abstracts flash talks
- BA03 Best abstracts flash talks
BA01 Best abstracts & Awards
Moderators: John Gribben (United Kingdom) & Nicolaus Kröger (Germany)
In summary, the authors conclude that pooled non-viral CRISPR knock-in screens allow highly parallel assessment and functional characterization of hundreds of different synthetic cell states. With the inclusion of clinically relevant screening modalities, candidate genes were nominated that can synthetically re-write the cellular state of CAR-T cells in response to repetitive antigen exposure or tonic signaling. They therefore have the potential to program more effective CAR T cell therapies for cancer.
----------------------------------------------------------------------------------------------------------------------------
Commensal short-chain fatty acids (SCFAs) are epigenetic and metabolic modifiers. They therefore have therapeutic potential in the context of adoptive cancer immunotherapy. The study provides new insights into the microbiome-CAR-T cell interface. These findings could be used to improve the efficacy of engineered CAR-T cell products.
----------------------------------------------------------------------------------------------------------------------------
This model is able to recapitulate the efficacy and safety aspect of CAR-T cell therapy. This will allow for a better understanding of the role of TME in hampering the efficacy in solid tumors. And it allows new insights into the pathogenesis of CRS in a controllable and fully human setting.
----------------------------------------------------------------------------------------------------------------------------
This year's meeting covered a wide range of topics. In turn, VJHemOnc did interviews on the following topics such as deep science, translational, clinical and commercial development in the field of CAR-T. See these posts on the VJHemOnc events page
BA02 Best abstracts flash talks
Moderators: Monica Casucci (Italy) & André Baruchel (France)
The authors have successfully generated highly specific dual-targeting CAR-T cells. They used optimal antigen binding strengths and split the T cell activation signals into two simultaneously expressed CARs. Their results demonstrate the possibility of safe and specific targeting of tumor-specific antigen combinations such as CD38 and CD138 in MM.
----------------------------------------------------------------------------------------------------------------------------
The study results suggest that transient expression of an epigenome editor is a novel and effective approach to specifically modulate the PD1 inhibitory pathway in CAR-T cells. With the first in vitro characterizations, the authors indicate that epiCART are functionally indistinguishable from unmodified parental CAR T cells. The authors expect that future exploitation of their in vivo efficacy, as well as DEM-associated off-target effects, will reveal the full potential of epiCART cells as novel immunotherapeutic agents to overcome tumor-associated immunosuppression.
----------------------------------------------------------------------------------------------------------------------------
The study results indicate that supernatants from activated BCMA-CAR T cells arrest myeloerythroid differentiation. For the study authors, this indicates a paracrine inhibition of normal hematopoiesis in vitro. "Particularly under spCAR conditions, differentiated HSCs lead to more immature myeloid populations at the phenotypic and transcriptomic levels." For the authors, their study is one of the first to provide molecular insight into cytopenias produced by BCMA-CAR T cells.
----------------------------------------------------------------------------------------------------------------------------
This year's meeting covered a wide range of topics. In turn, VJHemOnc did interviews on the following topics such as deep science, translational, clinical and commercial development in the field of CAR-T. See these posts on the VJHemOnc events page
BA03 Best abstracts flash talks
Moderators: Hermann Einsele (Germany) & Maria Themeli (Netherlands)
According to the authors, blocking N-glycosylation with 2DG reduces the immunosuppressive function of tumor microenvironment cells. This leads to increased activity of CEA-CAR T cells not only against cell lines but also against primary patient-derived organoids.
----------------------------------------------------------------------------------------------------------------------------
According to the authors, these data demonstrate that non-targeted (LV/SB) and targeted (KI) CAR insertion results in different patterns of CAR expression and regulation, and translates into differential antitumor reactivity. Targeted CAR AIs may be preferable for targeting high-density antigens to tumor cells, according to the authors. These are tumor cells where CAR-T cells (produced by other gene transfer methods) appear to be more susceptible to the negative effects of overstimulation.
----------------------------------------------------------------------------------------------------------------------------
According to the authors, these preclinical data offer a proof-of-concept strategy to increase the therapeutic index of CD123 and CD33 targeting by CAR-CIK cells: the data show a powerful antitumor efficacy mediated by low-affinity Dual CAR-CIK cells with trans-acting costimulation without any relevant toxicity on HSPCs and endothelial cells.
----------------------------------------------------------------------------------------------------------------------------
According to the study results, T-cell dysfunction occurs early after treatment, possibly due to chronic antigen exposure. According to the study authors, the underlying mechanisms and kinetics of CAR-T cell dysfunction need to be addressed in order to unleash the full potential of CAR-T cell therapy in solid tumors.
----------------------------------------------------------------------------------------------------------------------------
The anti-CD117 CAR T cells engineered with the SB vector showed anti-leukemia activity and completely depleted healthy HSPC in vivo, according to the study authors. iC9 transgenes induced CAR T cell apoptosis and enabled rapid CAR T cell depletion, which could alternatively be achieved by mRNA electroporation of the anti-CD117 CAR. The authors conclude that the ability to control CAR-T cell pharmacokinetic properties is attractive to enable subsequent HSCT and terminate unexpected toxicities.
----------------------------------------------------------------------------------------------------------------------------
The authors conclude that the administration of ARI-0001 cells was feasible, safe, and effective in this cohort of patients with high-risk CLL or RT.
----------------------------------------------------------------------------------------------------------------------------
The study authors provide a proof-of-concept for the generation of highly potent universal CAR-T cells from healthy donors and AML patients. The authors believe that selection of suitable CAR adapters in terms of their conjugation chemistry and size allows CAR T cell activity to be tightly regulated against CD33, CD117, and CD371-expressing AML cells (and likely any other antigen expressed by tumor cells). to regulate.
----------------------------------------------------------------------------------------------------------------------------
This year's meeting covered a wide range of topics. In turn, VJHemOnc did interviews on the following topics such as deep science, translational, clinical and commercial development in the field of CAR-T. See these posts on the VJHemOnc events page