Langerhans-type dendritic cells electroporated with TRP-2 mRNA stimulate cellular immunity against melanoma: Results of a phase I vaccine trial

Oncoimmunology
David J ChungJames W Young

Abstract

Purpose: We conducted a phase I vaccine trial to determine safety, toxicity, and immunogenicity of autologous Langerhans-type dendritic cells (LCs), electroporated with murine tyrosinase-related peptide-2 (mTRP2) mRNA in patients with resected AJCC stage IIB, IIC, III, or IV (MIa) melanoma. Experimental Design: Nine patients received a priming immunization plus four boosters at three week intervals. Vaccines comprised 10 × 106 mRNA-electroporated LCs, based on absolute number of CD83+CD86brightHLA-DRbrightCD14neg LCs by flow cytometry. Initial vaccines used freshly generated LCs, whereas booster vaccines used viably thawed cells from the cryopreserved initial product. Post-vaccination assessments included evaluation of delayed-type hypersensitivity (DTH) reactions after booster vaccines and immune response assays at one and three months after the final vaccine. Results: All patients developed mild DTH reactions at injection sites after booster vaccines, but there were no toxicities exceeding grade 1 (CTCAE, v4.0). At one and three months post-vaccination, antigen-specific CD4 and CD8 T cells increased secretion of proinflammatory cytokines (IFN-γ, IL-2, and TNF-α), above pre-vaccine levels, and also upregulated the cytotoxicity...Continue Reading

References

Dec 1, 1996·The Journal of Experimental Medicine·R F WangS A Rosenberg
Sep 17, 1998·The Journal of Clinical Investigation·L W WeberA N Houghton
Dec 10, 1999·The Journal of Experimental Medicine·W B BowneA N Houghton
Sep 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sylvie BeaulieuSvetlana Mojsov
Mar 1, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Emanuela RomanoJames W Young
Sep 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jianda YuanSacha Gnjatic
Sep 29, 2011·Journal of Immunological Methods·Harlan RobinsKaren Cerosaletti
Mar 23, 2012·Nature Reviews. Cancer·Karolina Palucka, Jacques Banchereau
Oct 26, 2013·Nature Communications·Christopher S CarlsonHarlan Robins
Apr 2, 2014·The Journal of Experimental Medicine·Xiaozhou FanJames P Allison
Apr 30, 2014·Cancer Immunology Research·Derek Ng TangPadmanee Sharma
May 30, 2014·Science Translational Medicine·Edward ChaLawrence Fong
Dec 20, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Geoffrey T GibneyJeffrey S Weber
Feb 5, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Debraj GuhaThakurtaCharles G Drake
Feb 11, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Dirk SchadendorfJedd D Wolchok
Feb 26, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michele MaioJedd D Wolchok
Sep 26, 2015·Molecular Oncology·Ilan KirschHarlan Robins
Mar 2, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sofie WilgenhofBart Neyns

❮ Previous
Next ❯

Citations

Oct 28, 2019·Oncoimmunology·Jenny SprootenAbhishek D Garg
May 6, 2020·Acta Pharmacologica Sinica·Yang-Zhuo GuXiang-Rong Song
Jan 13, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jessica LiegelDavid Avigan

❮ Previous
Next ❯

Methods Mentioned

BETA
surgical resection
flow cytometry
Assay

Clinical Trials Mentioned

NCT01456104

Software Mentioned

Prism
GraphPad

Related Concepts

Related Feeds

Cancer Immunotherapy

Cancer immunotherapy is an important field of research that is looking at controlling cancer and tumor growth by activating the individuals own immune system. Recent studies have utilized chimeric antigen receptor t-cell therapy, immune checkpoint inhibitors and neoantigen vaccines. Discover the latest research on cancer immunotherapy here.