title: Chemical castration of melanoma patients does not increase the frequency of tumor-specific CD4 and CD8 T cells after peptide vaccination.
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.
authors.affiliation: M.D. Anderson Cancer Center, University of Texas, Houston, TX 77054, USA. lmvence@mdanderson.org
authors.forename: Luis M
authors.initials: LM
authors.lastname: Vence
authors.forename: Chiyu
authors.initials: C
authors.lastname: Wang
authors.forename: Himabindu
authors.initials: H
authors.lastname: Pappu
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Anson
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Patel
authors.forename: Priscilla
authors.initials: P
authors.lastname: Miller
authors.forename: Roland
authors.initials: R
authors.lastname: Bassett
authors.forename: Gregory
authors.initials: G
authors.lastname: Lizee
authors.forename: Willem W
authors.initials: WW
authors.lastname: Overwijk
authors.forename: Krishna
authors.initials: K
authors.lastname: Komanduri
authors.forename: Cara
authors.initials: C
authors.lastname: Benjamin
authors.forename: Gladys
authors.initials: G
authors.lastname: Alvarado
authors.forename: Sapna P
authors.initials: SP
authors.lastname: Patel
authors.forename: Kevin
authors.initials: K
authors.lastname: Kim
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Papadopoulos
authors.forename: Agop Y
authors.initials: AY
authors.lastname: Bedikian
authors.forename: Jade
authors.initials: J
authors.lastname: Homsi
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Hwu
authors.forename: Richard
authors.initials: R
authors.lastname: Boyd
authors.forename: Laszlo
authors.initials: L
authors.lastname: Radvanyi
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D016729:Leuprolide / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology; D009367:Neoplasm Staging; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*; D055815:Young Adult; D058951:gp100 Melanoma Antigen / Q000737:chemistry / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D019496:Cancer Vaccines; D015851:Interleukin-7; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; D022223:Vaccines, Subunit; D058951:gp100 Melanoma Antigen; D016729:Leuprolide