Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: Clinical and immune responses in 35 patients

John M. Timmerman, Debra K. Czerwinski, Thomas A. Davis, Frank J. Hsu, Claudia Benike, Zheng Mei Hao, Behnaz Taidi, Ranjani Rajapaksa, Clemens B. Caspar, Craig Okada, Adrienne Van Beckhoven, Tina Marie Liles, Edgar G. Engleman, Ronald Levy

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1517-1526
Number of pages10
JournalBlood
Volume99
Issue number5
DOIs
StatePublished - Mar 1 2002
Externally publishedYes

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B-Cell Lymphoma
Dendritic Cells
Tumors
Vaccination
Cells
Neoplasms
T-cells
Chemotherapy
T-Lymphocytes
Active Immunotherapy
Drug Therapy
Follicular Lymphoma
Residual Neoplasm
Phosphorylation
Tyrosine
Disease Progression
Anti-Idiotypic Antibodies
Lymphoma
Appointments and Schedules
Carrier Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Timmerman, J. M., Czerwinski, D. K., Davis, T. A., Hsu, F. J., Benike, C., Hao, Z. M., ... Levy, R. (2002). Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: Clinical and immune responses in 35 patients. Blood, 99(5), 1517-1526. https://doi.org/10.1182/blood.V99.5.1517

Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma : Clinical and immune responses in 35 patients. / Timmerman, John M.; Czerwinski, Debra K.; Davis, Thomas A.; Hsu, Frank J.; Benike, Claudia; Hao, Zheng Mei; Taidi, Behnaz; Rajapaksa, Ranjani; Caspar, Clemens B.; Okada, Craig; Van Beckhoven, Adrienne; Liles, Tina Marie; Engleman, Edgar G.; Levy, Ronald.

In: Blood, Vol. 99, No. 5, 01.03.2002, p. 1517-1526.

Research output: Contribution to journalArticle

Timmerman, JM, Czerwinski, DK, Davis, TA, Hsu, FJ, Benike, C, Hao, ZM, Taidi, B, Rajapaksa, R, Caspar, CB, Okada, C, Van Beckhoven, A, Liles, TM, Engleman, EG & Levy, R 2002, 'Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: Clinical and immune responses in 35 patients', Blood, vol. 99, no. 5, pp. 1517-1526. https://doi.org/10.1182/blood.V99.5.1517
Timmerman JM, Czerwinski DK, Davis TA, Hsu FJ, Benike C, Hao ZM et al. Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: Clinical and immune responses in 35 patients. Blood. 2002 Mar 1;99(5):1517-1526. https://doi.org/10.1182/blood.V99.5.1517
Timmerman, John M. ; Czerwinski, Debra K. ; Davis, Thomas A. ; Hsu, Frank J. ; Benike, Claudia ; Hao, Zheng Mei ; Taidi, Behnaz ; Rajapaksa, Ranjani ; Caspar, Clemens B. ; Okada, Craig ; Van Beckhoven, Adrienne ; Liles, Tina Marie ; Engleman, Edgar G. ; Levy, Ronald. / Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma : Clinical and immune responses in 35 patients. In: Blood. 2002 ; Vol. 99, No. 5. pp. 1517-1526.
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abstract = "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.",
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AU - Okada, Craig

AU - Van Beckhoven, Adrienne

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