Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts.

Cartellieri M ，Feldmann A ，Koristka S ，Arndt C ，Loff S ，Ehninger A ，von Bonin M ，Bejestani EP ，Ehninger G ，Bachmann MP ... -  《Blood Cancer Journal》

Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology "UniCAR".

Feldmann A ，Arndt C ，Bergmann R ，Loff S ，Cartellieri M ，Bachmann D ，Aliperta R ，Hetzenecker M ，Ludwig F ，Albert S ，Ziller-Walter P ，Kegler A ，Koristka S ，Gärtner S ，Schmitz M ，Ehninger A ，Ehninger G ，Pietzsch J ，Steinbach J ，Bachmann M ... -  《-》

Development of A Chimeric Antigen Receptor Targeting C-Type Lectin-Like Molecule-1 for Human Acute Myeloid Leukemia.

Laborda E ，Mazagova M ，Shao S ，Wang X ，Quirino H ，Woods AK ，Hampton EN ，Rodgers DT ，Kim CH ，Schultz PG ，Young TS ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia.

Chimeric antigen receptor (CAR)-redirected T lymphocytes are a promising immunotherapeutic approach and object of pre-clinical evaluation for the treatment of acute myeloid leukemia (AML). We developed a CAR against CD123, overexpressed on AML blasts and leukemic stem cells. However, potential recognition of low CD123-positive healthy tissues, through the on-target, off-tumor effect, limits safe clinical employment of CAR-redirected T cells. Therefore, we evaluated the effect of context-dependent variables capable of modulating CAR T cell functional profiles, such as CAR binding affinity, CAR expression, and target antigen density. Computational structural biology tools allowed for the design of rational mutations in the anti-CD123 CAR antigen binding domain that altered CAR expression and CAR binding affinity without affecting the overall CAR design. We defined both lytic and activation antigen thresholds, with early cytotoxic activity unaffected by either CAR expression or CAR affinity tuning but later effector functions impaired by low CAR expression. Moreover, the anti-CD123 CAR safety profile was confirmed by lowering CAR binding affinity, corroborating CD123 is a good therapeutic target antigen. Overall, full dissection of these variables offers suitable anti-CD123 CAR design optimization for the treatment of AML.

Arcangeli S ，Rotiroti MC ，Bardelli M ，Simonelli L ，Magnani CF ，Biondi A ，Biagi E ，Tettamanti S ，Varani L ... -  《-》

In Vitro Pre-Clinical Validation of Suicide Gene Modified Anti-CD33 Redirected Chimeric Antigen Receptor T-Cells for Acute Myeloid Leukemia.

Minagawa K ，Jamil MO ，Al-Obaidi M ，Pereboeva L ，Salzman D ，Erba HP ，Lamb LS ，Bhatia R ，Mineishi S ，Di Stasi A ... -  《PLoS One》