Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients
Brigham and Women's Hospital · Harvard University · +10 more institutions
Abstract
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) functions as a negative regulator of endogenous and vaccine-induced antitumor immunity. The administration of fully human anti-CTLA-4 blocking monoclonal antibodies to advanced-cancer patients increases immune-mediated tumor destruction in some subjects. Nonetheless, patients that respond also frequently manifest serious inflammatory pathologies, raising the possibility that the therapeutic and toxic effects of CTLA-4 blockade might be linked. Here we show that periodic infusions of anti-CTLA-4 antibodies after vaccination with irradiated, autologous tumor cells engineered to secrete GM-CSF (GVAX) generate clinically meaningful antitumor immunity without…
Citation impact
- FWCI
- 16.25
- Percentile
- 100%
- References
- 43
Authors
20- FSF. Stephen Hodi
Brigham and Women's Hospital, Harvard University, Massachusetts General Hospital, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center
- MOMarcus O. Butler
Brigham and Women's Hospital, Harvard University, Massachusetts General Hospital, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center
- DADarryl A. Oble
Fox Chase Cancer Center, Bristol-Myers Squibb (Germany), Bristol-Myers Squibb (Italy)
- MVMichael V. Seiden
Fox Chase Cancer Center, Harvard University, Bristol-Myers Squibb (Germany), Massachusetts General Hospital, Bristol-Myers Squibb (Italy)
- FGFrank G. Haluska
Tufts Medical Center
Topics & keywords
- Immunology
- Medicine
- Immunotherapy
- Cytotoxic T cell
- Antigen
- FOXP3
- Antibody
- Cancer immunotherapy
- Good health and well-being