Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients

Ruggero Ridolfi, Massimiliano Petrini, Laura Fiammenghi, Monica Stefanelli, Laura Ridolfi, Michela Ballardini, Giuseppe Migliori, Angela Riccobon

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Abstract

Background: We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma. Methods: Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 μg/ml of autologous-tumor-lysate (ATL) or - homogenate (ATH) and 50 μg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC)(range 4.5 - 82 × 106) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2-26 × 106). Subcutaneous interleukin-2 (3 × 106 IU) was administered from days 3 to 7 of each treatment cycle. Results: Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SID (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19%) patients, or 4/13 (30.7%) considering mDC treatment only. 10/21 (47.6%) patients showed non progressive disease (NPD), with 7/13 (53.8%) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3 - 45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3-14) for the 11 DTH-negative patients (P <0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75%) and clinical outcome (70%). Conclusion: Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival.

Original languageEnglish
Article number36
JournalJournal of Translational Medicine
Volume4
DOIs
Publication statusPublished - Aug 16 2006

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Dendritic Cells
Melanoma
Vaccination
Survival
Tumors
Delayed Hypersensitivity
Immunization
T-cells
Neoplasm Antigens
Interleukin-2
Toxicity
Stabilization
Neoplasms
Sudden Infant Death
Interleukin-3
Autoantigens
keyhole-limpet hemocyanin
Therapeutics
T-Lymphocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients. / Ridolfi, Ruggero; Petrini, Massimiliano; Fiammenghi, Laura; Stefanelli, Monica; Ridolfi, Laura; Ballardini, Michela; Migliori, Giuseppe; Riccobon, Angela.

In: Journal of Translational Medicine, Vol. 4, 36, 16.08.2006.

Research output: Contribution to journalArticle

Ridolfi, Ruggero ; Petrini, Massimiliano ; Fiammenghi, Laura ; Stefanelli, Monica ; Ridolfi, Laura ; Ballardini, Michela ; Migliori, Giuseppe ; Riccobon, Angela. / Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients. In: Journal of Translational Medicine. 2006 ; Vol. 4.
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abstract = "Background: We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma. Methods: Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 μg/ml of autologous-tumor-lysate (ATL) or - homogenate (ATH) and 50 μg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC)(range 4.5 - 82 × 106) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2-26 × 106). Subcutaneous interleukin-2 (3 × 106 IU) was administered from days 3 to 7 of each treatment cycle. Results: Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SID (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19{\%}) patients, or 4/13 (30.7{\%}) considering mDC treatment only. 10/21 (47.6{\%}) patients showed non progressive disease (NPD), with 7/13 (53.8{\%}) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3 - 45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3-14) for the 11 DTH-negative patients (P <0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75{\%}) and clinical outcome (70{\%}). Conclusion: Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival.",
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AU - Ridolfi, Ruggero

AU - Petrini, Massimiliano

AU - Fiammenghi, Laura

AU - Stefanelli, Monica

AU - Ridolfi, Laura

AU - Ballardini, Michela

AU - Migliori, Giuseppe

AU - Riccobon, Angela

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N2 - Background: We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma. Methods: Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 μg/ml of autologous-tumor-lysate (ATL) or - homogenate (ATH) and 50 μg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC)(range 4.5 - 82 × 106) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2-26 × 106). Subcutaneous interleukin-2 (3 × 106 IU) was administered from days 3 to 7 of each treatment cycle. Results: Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SID (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19%) patients, or 4/13 (30.7%) considering mDC treatment only. 10/21 (47.6%) patients showed non progressive disease (NPD), with 7/13 (53.8%) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3 - 45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3-14) for the 11 DTH-negative patients (P <0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75%) and clinical outcome (70%). Conclusion: Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival.

AB - Background: We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma. Methods: Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 μg/ml of autologous-tumor-lysate (ATL) or - homogenate (ATH) and 50 μg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC)(range 4.5 - 82 × 106) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2-26 × 106). Subcutaneous interleukin-2 (3 × 106 IU) was administered from days 3 to 7 of each treatment cycle. Results: Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SID (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19%) patients, or 4/13 (30.7%) considering mDC treatment only. 10/21 (47.6%) patients showed non progressive disease (NPD), with 7/13 (53.8%) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3 - 45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3-14) for the 11 DTH-negative patients (P <0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75%) and clinical outcome (70%). Conclusion: Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival.

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