Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients.
Tumor-specific clonal immunoglobulin expressed by B-cell lymphomas (idiotype [Id]) can serve as a target for active immunotherapy. We have previously described the vaccination of 4 patients with follicular lymphoma using dendritic cells (DCs) pulsed with tumor-derived Id protein and now report on 35 patients treated using this approach. Among 10 initial patients with measurable lymphoma, 8 mounted T-cell proliferative anti-Id responses, and 4 had clinical responses--2 complete responses (CRs) (progression-free [PF] for 44 and 57 months after vaccination), 1 partial response (PR) (PF for 12 months), and 1 molecular response (PF for 75+ months). Subsequently, 25 additional patients were vaccinated after first chemotherapy, and 15 of 23 (65%) who completed the vaccination schedule mounted T-cell or humoral anti-Id responses. Induction of high-titer immunoglobulin G anti-Id antibodies required coupling of Id to the immunogenic carrier protein keyhole limpet hemocyanin (Id-KLH). These antibodies could bind to and induce tyrosine phosphorylation in autologous tumor cells. Among 18 patients with residual tumor at the time of vaccination, 4 (22%) had tumor regression, and 16 of 23 patients (70%) remain without tumor progression at a median of 43 months after chemotherapy. Six patients with disease progression after primary DC vaccination received booster injections of Id-KLH protein, and tumor regression was observed in 3 of them (2 CRs and 1 PR). We conclude that Id-pulsed DC vaccination can induce T-cell and humoral anti-Id immune responses and durable tumor regression. Subsequent boosting with Id-KLH can lead to tumor regression despite apparent resistance to the primary DC vaccine.
Timmerman
John M
JM
Division of Oncology, Department of Medicine, Stanford University School of Medicine, CA, USA.
Czerwinski
Debra K
DK
Davis
Thomas A
TA
Hsu
Frank J
FJ
Benike
Claudia
C
Hao
Zheng Mei
ZM
Taidi
Behnaz
B
Rajapaksa
Ranjani
R
Caspar
Clemens B
CB
Okada
Craig Y
CY
van Beckhoven
Adrienne
A
Liles
Tina Marie
TM
Engleman
Edgar G
EG
Levy
Ronald
R
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005500:Follow-Up Studies; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology* / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive / Q000379:methods; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D000888:Antibodies, Anti-Idiotypic; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin