Integrating Immune Checkpoint Blockade with Anti-Neo/Mutated Antigens Reactivity to Increase the Clinical Outcome of Immunotherapy.
Antibodies to immune checkpoints have entered the clinical arena and have been shown to provide a clinical benefit for metastatic melanoma and, possibly, for other tumors as well. In this review paper we summarize this therapeutic activity and underline the functional mechanisms that may be involved. Among them, we discuss the so far neglected role of tumor-associated antigens (TAAs) deriving from tumor somatic mutations and summarize the results of recent trials showing the immunogenic strength of such TAAs which can be specifically targeted by T cells activated by immune checkpoint antibodies. Finally we discuss new immunotherapy approaches that involve the combination of self/shared- or neo-TAAs-based vaccines and immune checkpoint blockade antibodies, to increase the clinical response of metastatic melanoma patients.
Italian Network for Bio-therapy of Tumors-(NIBIT)-Laboratory, c/o University Hospital of Siena, V. le Bracci, 16, Siena 53100, Italy. giorgio.parmiani@fastwebnet.it.|Division of Medical Oncology and Immunotherapy, University Hospital of Siena, V. le Bracci, 16, Siena 53100, Italy. giorgio.parmiani@fastwebnet.it.
Giorgio
G
Parmiani
Italian Network for Bio-therapy of Tumors-(NIBIT)-Laboratory, c/o University Hospital of Siena, V. le Bracci, 16, Siena 53100, Italy. crimaccalli@gmail.com.|Division of Medical Oncology and Immunotherapy, University Hospital of Siena, V. le Bracci, 16, Siena 53100, Italy. crimaccalli@gmail.com.
Cristina
C
Maccalli
Division of Medical Oncology and Immunotherapy, University Hospital of Siena, V. le Bracci, 16, Siena 53100, Italy. mmaiocro@gmail.com.
Michele
M
Maio
immune checkpoint antibodies; melanoma immunotherapy; neo/mutated tumor antigens