Chemical castration of melanoma patients does not increase the frequency of tumor-specific CD4 and CD8 T cells after peptide vaccination

Luis M. Vence, Chiyu Wang, Himabindu Pappu, Ryan E. Anson, Tejal A. Patel, Priscilla Miller, Roland Bassett, Gregory Lizee, Willem W. Overwijk, Krishna V Komanduri, Cara Benjamin, Gladys Alvarado, Sapna P. Patel, Kevin Kim, Nicholas E. Papadopoulos, Agop Y. Bedikian, Jade Homsi, Wen Jen Hwu, Richard Boyd, Laszlo Radvanyi & 1 others Patrick Hwu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Peptide vaccination against tumor-associated antigens remains one of the most common methods of immunization in cancer vaccine clinical trials. Although peptide vaccination has been reported to increase circulating antigen-specific T-cells, they have had limited clinical efficacy and there is a necessity to increase their capacity to generate strong antitumor responses. We sought to improve the clinical efficacy of peptide-based vaccines in cancer immunotherapy of metastatic melanoma using a LHRH agonist (leuprolide) as adjuvant. Seventy HLA-A*0201 stage IIb-IV melanoma patients were vaccinated with class I HLA-A*0201-restricted gp100209-2M peptide and stratified for HLA-DP4 restriction. HLA-DP4 patients were also vaccinated with class II HLA-DP4-restricted MAGE-3243-258 peptide. Patients from both groups were randomized to receive 2 doses of leuprolide or not. Here we report the increase in PBMC TREC levels at week 24 after peptide vaccination, which was independent of the leuprolide treatment. This change was mirrored by a small increase in the TREC-enriched CD8CD45RAROCD27CD103, but not the TREC-enriched CD4CD45RAROCD31 T-cell population. Serum concentration of 2 important factors for thymopoiesis was measured: insulin growth factor 1 (IGF-1) levels were not changed, whereas a moderate increase in IL-7 levels was noted in the sera of all patients 6 weeks after vaccination. Increased expression of CD127 (IL-7 receptor-α) at week 24, compared with baseline, was only seen in the CD8CD45RAROCD27CD103 T-cell population. Our results suggest that leuprolide has no effect on thymic output when used as peptide vaccine adjuvant, but IFA-based peptide vaccination may unexpectedly affect the thymus by increasing thymic output of new T cells.

Original languageEnglish
Pages (from-to)276-286
Number of pages11
JournalJournal of Immunotherapy
Volume36
Issue number4
DOIs
StatePublished - May 1 2013

Fingerprint

Castration
Leuprolide
Melanoma
Vaccination
T-Lymphocytes
Peptides
Neoplasms
Subunit Vaccines
Interleukin-7 Receptors
Interleukin-7
Cancer Vaccines
Neoplasm Antigens
Serum
Gonadotropin-Releasing Hormone
Immunotherapy
Thymus Gland
Population
Immunization
Intercellular Signaling Peptides and Proteins
Clinical Trials

Keywords

  • IL-7
  • LHRH agonist
  • melanoma
  • peptide vaccination
  • TREC

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology

Cite this

Chemical castration of melanoma patients does not increase the frequency of tumor-specific CD4 and CD8 T cells after peptide vaccination. / Vence, Luis M.; Wang, Chiyu; Pappu, Himabindu; Anson, Ryan E.; Patel, Tejal A.; Miller, Priscilla; Bassett, Roland; Lizee, Gregory; Overwijk, Willem W.; Komanduri, Krishna V; Benjamin, Cara; Alvarado, Gladys; Patel, Sapna P.; Kim, Kevin; Papadopoulos, Nicholas E.; Bedikian, Agop Y.; Homsi, Jade; Hwu, Wen Jen; Boyd, Richard; Radvanyi, Laszlo; Hwu, Patrick.

In: Journal of Immunotherapy, Vol. 36, No. 4, 01.05.2013, p. 276-286.

Research output: Contribution to journalArticle

Vence, LM, Wang, C, Pappu, H, Anson, RE, Patel, TA, Miller, P, Bassett, R, Lizee, G, Overwijk, WW, Komanduri, KV, Benjamin, C, Alvarado, G, Patel, SP, Kim, K, Papadopoulos, NE, Bedikian, AY, Homsi, J, Hwu, WJ, Boyd, R, Radvanyi, L & Hwu, P 2013, 'Chemical castration of melanoma patients does not increase the frequency of tumor-specific CD4 and CD8 T cells after peptide vaccination', Journal of Immunotherapy, vol. 36, no. 4, pp. 276-286. https://doi.org/10.1097/CJI.0b013e31829419f3
Vence, Luis M. ; Wang, Chiyu ; Pappu, Himabindu ; Anson, Ryan E. ; Patel, Tejal A. ; Miller, Priscilla ; Bassett, Roland ; Lizee, Gregory ; Overwijk, Willem W. ; Komanduri, Krishna V ; Benjamin, Cara ; Alvarado, Gladys ; Patel, Sapna P. ; Kim, Kevin ; Papadopoulos, Nicholas E. ; Bedikian, Agop Y. ; Homsi, Jade ; Hwu, Wen Jen ; Boyd, Richard ; Radvanyi, Laszlo ; Hwu, Patrick. / Chemical castration of melanoma patients does not increase the frequency of tumor-specific CD4 and CD8 T cells after peptide vaccination. In: Journal of Immunotherapy. 2013 ; Vol. 36, No. 4. pp. 276-286.
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AU - Bassett, Roland

AU - Lizee, Gregory

AU - Overwijk, Willem W.

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AU - Benjamin, Cara

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AU - Kim, Kevin

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