1 collaborations with dr. pi terasaki 1.natural anti-human lymphocyte cytotoxic antibodies in...
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Collaborations with Dr. PI Terasaki
1. Natural anti-human lymphocyte cytotoxic antibodies in mammalian sera (Ferrone S….., Terasaki PI: i) Transplantation. 1973;16:287-94. ii) Tissue Antigens.
1973;3:88-94).
2. Characterization of serum HLA antigens Ferrone S….., Terasaki PI: i) Tissue Antigens: 1975;5:41-7. ii) Immunol Commun. 1972;1:77-91).
3. HLA phenotyping of cultured B lymphoid cells (Ferrone S….., Terasaki PI: i) J Clin Invest. 1975;55:388-94. ii) Transplantation. 1976;22:61-8)
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HLA class I antigens in tumor cells
Clinical applications
1991-20111978-1990 2012-
Hybridoma methodology
Many HLA class I-specific mAbs
Renaissance phaseIndifferent phaseEnthusiasm phase
Anti-CTLA4
Anti-PD-1
Anti-PD-L1
Information in the literature
1. Defects in HLA class I antigens found in most if not all malignancies analyzed
2. Characterization of the multiple molecular mechanisms underlying HLA class I antigen defects in malignant cells
3. Assessment of the clinical significance of the HLA class I antigen defects found in malignant cells
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HLA class I antigens in tumor cells
Clinical applications
1991-20111978-1990 2012-
Hybridoma methodology
Many HLA class I-specific mAbs
Renaissance phaseIndifferent phaseEnthusiasm phase
Anti-CTLA4
Anti-PD-1
Anti-PD-L1
HLA Class I Antigen Processing in Tumors
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ERK1/2 activation in melanoma cells with a constitutively active BRAF-mutated
HLA Class I antigen up-regulation by BRAF-I and IFNα-2b on melanoma cells with an
active BRAF-mutated
SK-MEL-37
IFNα-2b
BRAF-I
HLA Class I mAb TP25.99 HLA B/C mAb B1.23.2
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HLA Class I APM component up-regulation by EGFR-specific mAb cetuximab in the head and neck
squamous cancer cell line JHU-029
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HLA-A2-MAGE-3 peptide complex up-regulation by EGFR-specific mAb cetuximab in the head and neck
squamous cancer cell line JHU-029
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HLA Class I APM component up-regulation by docetaxel in human cancer cell lines
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Increased sensitivity to cognate CTL of human cancer cell lines treated with docetaxel
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HLA Class I APM component up-regulation by radiation in human cancer cell lines
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HLA class I antigen expression by malignant cells is modulated by signaling transduction pathways, chemotherapy and radiotherapy.
These changes are associated with an increased T cell recognition and destruction of cancer cells.
Conclusions
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HLA class I antigens in tumor cells
Clinical applications
1991-20111978-1990 2012-
Hybridoma methodology
Many HLA class I-specific mAbs
Renaissance phaseIndifferent phaseEnthusiasm phase
Anti-CTLA4
Anti-PD-1
Anti-PD-L1
Targeting Immunoregulatory Molecules in Cancer
15Figure adapted from A. Ribas, NEJM, 2012
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Immunotherapy with check point molecule-specific mAb induces dramatic and long lasting responses, but only in up to 30% of patients.
These findings emphasize the need to identify biomarkers to select patients who may benefit from this therapy
HLA class I antigen expression by malignant cells may be a useful biomarker since defects in HLA class I antigen expression may protect tumor cells.
Conclusions
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Soldano Ferrone, MD, PhD
Departments of Surgey and Orthopedic SurgeryMassachusetts General Hospital,Harvard Medical School,Boston, MA (USA)
HLA class I antigen defects in malignant cells
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Acknowledgements
Francesco Sabbatino, MD, PhD
Cristina R. Ferrone, MD
James Hodge, PhD (NCI, Bethesda, MD)
Robert L. Ferris, MD, PhD (University of Pittsburgh, Pittsburgh, PA)
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Model of HLA Class I APM component up-regulation by docetaxel in human cancer cell lines
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HLA Class I antigen up-regulation by EGFR-specific mAb cetuximab on the head and
neck squamous cancer cell line JHU-029