News

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Apr 2016
NEW PUBLICATION

Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model

Mar 2016
NEW PUBLICATION

Humanized mouse G6 anti-idiotypic monoclonal antibody has therapeutic potential against IGHV1-69 germline gene-based B-CLL

Feb 2016
NEW PUBLICATION

IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity.


Announcements

Launch of Humanized Mouse Program

The Marasco Lab Humanized Mouse Program is open to the research community
Read more

www.humouse.org

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Project Highlight:
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
 

 

 

Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model
  1. Anti-PD-L1-secreting anti-CAIX CAR T cells show markedly enhanced anti-tumor effect with decreased tumor growth and weight
  2. Locally secreted IgG1 is retained at the tumor site, not rapidly diffused into the blood circulation
  3. 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
  4. 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.