6 / 26
Immunology 2018
J u l y 0 5 - 0 7 , 2 0 1 8
V i e n n a , A u s t r i a
Page 37
Journal of Clinical Immunology and Allergy
ISSN 2471-304X
1 5
t h
I n t e r n a t i o n a l C o n f e r e n c e o n
Immunology
Background:
A recently completed Phase I/2a trials using a HLA-A2 XBP1,
CD138 and CS1 multipeptide vaccine in smoldering multiple myeloma (SMM)
patients demonstrated induction of antigen-specific CD8+ memory CTL. The
antigens-specific Th1 type responses were further enhanced in the patients
in combination with lenalidomide, as evidenced by increased Tetramer+ CTL
and functional immune responses. Beyond myeloma, the multipeptide vaccine
is in clinical trial to treat the patients with triple negative breast cancer by
overexpression of the antigens in various solid tumours.
Objective:
To expand therapeutic opportunities beyond HLA-A2 specificity, we
have identified novel immunogenic peptides to HLA-A24 molecule, which is
the second most dominant MHC Class I molecule in North America and the
most frequent MHC Class I molecule in Asia.
Findings:
Individual HLA-A24 peptides, XBP1 UN
185-193
(I S P W I L A V L), XBP1
SP
223-231
(V Y P E G P S S L), CD138
265-273
(I F A V C L V G F) and CS1
240-248
(L F
V L G L F L W), induced the antigens-specific CTL with anti-tumour immune
responses against both MM and solid tumours in an HLA-A24 restricted
manner. CTL phenotypic characterization revealed the upregulation of immune
costimulatory (OX40, GITR) and checkpoint antigens (PD1, CTLA, LAG3,
TIM3). Peptide-specific CTL treated with clinical grade anti-OX40 or anti-PD1
displayed enhanced cytotoxicity and Th1 cytokines production to tumour cells.
Furthermore, the central memory (CD45RO
+
CCR7
+
) CTL subset demonstrated
enhanced functional activities to the respective tumour cells, with the highest
increases induced by the OX40 stimulation or PD1 inhibition.
Significance:
These results highlight the potential therapeutic application of a
cocktail of HLA-A24 XBP1/CD138/CS1 peptides to evoke the antigens-specific
CTL with a broad spectrum of responses against tumor and provide the
framework for a combination immunotherapy with multipeptide vaccination
and immune agonist or checkpoint inhibitor to inhibit immune suppression and
enhance tumor-specific memory CTL activities in cancer patients.
Biography
Jooeun Bae has completed her PhD from Virginia Polytechnic
Institute and State University and Postdoctoral studies from
Harvard Medical School (Boston, MA) and Rush University
Medical Center (Chicago, IL). She worked as an Assistant
Professor at Rush University Medical Center, Senior Research
Scientist at Cell Genesys Inc. (San Francisco, CA) and currently
working as an Instructor at Dana-Farber Cancer Institute,
Harvard Medical School. Her expertise has been Cancer
Immunology and Immunotherapy, focused on discovery and
development of cancer vaccine, which are currently in multiple
clinical trials. She has published more than 22 papers in
reputed journals and has been serving as an Editorial Board
Member of repute
.
Jooeun_bae@dfci.harvard.eduCombination immunotherapy enhanced anti-tumor activities
of XBP1, CD138 and CS1 antigens-specific CD8
+
cytotoxic T
lymphocytes against multiple myeloma and solid tumors
Jooeun Bae, Teru Hideshima, Nikhil Munshi and Kenneth Anderson
Dana-Farber Cancer Institute, Harvard Medical School, USA
Jooeun Bae et al., Insights Allergy Asthma Bronchitis 2018, Volume: 4
DOI: 10.21767/2471-304X-C1-002