Immunization with Melan-A peptide-pulsed peripheral blood mononuclear cells plus recombinant human interleukin-12 induces clinical activity and T-cell responses in advanced melanoma.
OBJECTIVE
Preclinical studies showed that immunization with peripheral blood mononuclear cells (PBMC) loaded with tumor antigen peptides plus interleukin-12 (IL-12) induced CD8+ T-cell responses and tumor rejection. We recently determined that recombinant human (rh) IL-12 at 30 to 100 ng/kg is effective as a vaccine adjuvant in patients. A phase II study of immunization with Melan-A peptide-pulsed PBMC + rhIL-12 was conducted in 20 patients with advanced melanoma.


METHODS
Patients were HLA-A2-positive and had documented Melan-A expression. Immunization was performed every 3 weeks with clinical re-evaluation every three cycles. Immune responses were measured by ELISpot assay before and after treatment and through the first three cycles, and were correlated with clinical outcome.


RESULTS
Most patients had received prior therapy and had visceral metastases. Nonetheless, two patients achieved a complete response, five patients achieved a minor or mixed response, and four patients had stable disease. The median survival was 12.25 months for all patients and was not yet reached for those with a normal lactate dehydrogenase. There were no grade 3 or 4 toxicities. Measurement of specific CD8+ T-cell responses by direct ex vivo ELISpot revealed a significant increase in interferon gamma-producing T cells against Melan-A (P =.015) after vaccination, but not against an Epstein-Barr virus control peptide (P =.86). There was a correlation between the magnitude of the increase in Melan-A-specific cells and clinical response (P =.046).


CONCLUSIONS
This immunization approach may be more straightforward than dendritic cell strategies and seems to have clinical activity that can be correlated to a biologic end point.
Peterson
Amy C
AC
Department of Pathology, University of Chicago, IL 60637, USA.
Harlin
Helena
H
Gajewski
Thomas F
TF
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D019496:Cancer Vaccines; D005260:Female; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma; D018664:Interleukin-12 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma