Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model
Humanized mouse G6 anti-idiotypic monoclonal antibody has therapeutic potential against IGHV1-69 germline gene-based B-CLL
IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity.
Antibody Engineering: Anti-CAIX CAR T cells secreting anti-PD-L1 IgG1 or IgG4 can diminish T cell exhaustion and improve CAR T cell treatment of ccRCC in vivo
- Anti-PD-L1-secreting anti-CAIX CAR T cells show markedly enhanced anti-tumor effect with decreased tumor growth and weight
- Locally secreted IgG1 is retained at the tumor site, not rapidly diffused into the blood circulation
- Second-generation anti-CAIX CAR T cells secreting anti-PD-L1 IgGs retained in the RCC milieu show reduced T cell exhaustion and enhanced anti-tumor activity
- Secreted anti-PD-L1 IgG1 or IgG4 can interact with PD-L1+ RCC cells; reverse upregulation of exhaustion markers PD-1, TIM-3 and LAG-3; and restore tumor cell killing
T cells were transduced with the lentiviruses to generate anti-CAIX CAR T cells, which are able to recognize CAIX positive RCC and also secrete anti-PD-L1 IgG1 or IgG4 in the tumor microenvironment to block PD-1/PD-L1-induced T cell exhaustion.