HSP70i Q435A to subdue autoimmunity and support anti-tumor responses.

Autor: Jaishankar D; Department of Dermatology & Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. jaishank@musc.edu.; Department of Surgery, Medical University of South Carolina, Charleston, SC, USA. jaishank@musc.edu., Cosgrove C; Department of Dermatology & Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA., Ramesh P; Department of Dermatology & Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA., Mahon J; Cardinal Bernardin Cancer Center, Loyola University Chicago, Chicago, IL, USA., Shivde R; Department of Dermatology & Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA., Dellacecca ER; Department of Dermatology & Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA., Yang SF; Department of Otolaryngology - Head and Neck Surgery, Loyola University Medical Center, Maywood, IL, USA., Mosenson J; Cardinal Bernardin Cancer Center, Loyola University Chicago, Chicago, IL, USA., Guevara-Patiño JA; Department of Surgery, Loyola University Medical Center, Maywood, IL, USA.; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Le Poole IC; Department of Dermatology & Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. caroline.lepoole@northwestern.edu.; Cardinal Bernardin Cancer Center, Loyola University Chicago, Chicago, IL, USA. caroline.lepoole@northwestern.edu.; Department of Microbiology & Immunology, Northwestern University, Chicago, IL, USA. caroline.lepoole@northwestern.edu.
Jazyk: angličtina
Zdroj: Cell stress & chaperones [Cell Stress Chaperones] 2021 Sep; Vol. 26 (5), pp. 845-857. Date of Electronic Publication: 2021 Sep 20.
DOI: 10.1007/s12192-021-01229-x
Abstrakt: Developing immunosuppressive therapies for autoimmune diseases comes with a caveat that immunosuppression may promote the risk of developing other conditions or diseases. We have previously shown that biolistic delivery of an expression construct encoding inducible HSP70 (HSP70i) with one amino acid modification in the dendritic cell (DC) activating moiety 435-445 (HSP70i Q435A ) to mouse skin resulted in significant immunosuppressive activity of autoimmune vitiligo, associated with fewer tissue infiltrating T cells. To prepare HSP70i Q435A as a potential therapeutic for autoimmune vitiligo, in this study we evaluated whether and how biolistic delivery of HSP70i Q435A in mice affects anti-tumor responses. We found that HSP70i Q435A in fact supports anti-tumor responses in melanoma-challenged C57BL/6 mice. Biolistic delivery of the HSP70i Q435A -encoding construct to mice elicited significant anti-HSP70 titers, and anti-HSP70 IgG and IgM antibodies recognize surface-expressed and cytoplasmic HSP70i in human and mouse melanoma cells. A peptide scan revealed that the anti-HSP70 antibodies recognize a specific C-terminal motif within the HSP70i protein. The antibodies elicited surface CD107A expression among mouse NK cells, representative of antibody-mediated cellular cytotoxicity (ADCC), supporting the concept, that HSP70i Q435A -encoding DNA elicits a humoral response to the stress protein expressed selectively on the surface of melanoma cells. Thus, besides limiting autoimmunity and inflammation, HSP70i Q435A elicits humoral responses that limit tumor growth and may be used in conjunction with immune checkpoint inhibitors to not only control tumor but to also limit adverse events following tumor immunotherapy.
(© 2021. Cell Stress Society International.)
Databáze: MEDLINE
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