Clinical experience with autologous tumor cell lines for patient- specific vaccine therapy in metastatic melanoma

Robert O. Dillman, Shankar K. Nayak, Neil M. Barth, Cristina Deleon, Lee Schwartzberg, Lynn E. Spitler, Curtis Church, Audrey A. O'Connor, Linda D. Beutel

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Because of their patient specificity and proliferative capacity, tumor cell lines established from autologous metastatic melanoma tumor samples may be an excellent immunogen for patient-specific vaccine therapy. Between October 1990 and July 1996, the Hoag Cancer Center cell biology laboratory received 136 fresh metastatic melanoma samples from 122 different patients. Tumor cell lines were successfully established for 92 of 136 samples (68%), for 87 of 122 patients (71%). Successful cultures were expanded to 108 cells (total culture time about 8 weeks), confirmed to be sterile, irradiated, and stored frozen in aliquots of 107 cells. Vaccines were prepared from 72 lines, and 62 vaccines were used in 57 different patients. Subcutaneous vaccination took place on weeks 1, 2 and 3, and then monthly for a total of 6 months. A delayed tumor hypersensitivity skin test (DTH) was administered at week zero and week 4. Various adjuvants were co-administered including BCG, α- or γ-interferon, and GM-CSF. Patients were monitored for failure-free survival (FFS) and overall survival (OS) from the date of the first vaccination. Follow-up data is available for 52 patients, 27 who had no evident disease (NED) at the time of vaccination and 25 who had metastatic disease at the time of treatment. There were two partial responses which persisted 11.9 and 39.8+ months among the 25 patients who had detectable metastatic disease whun treatment was initiated (8%, 1 to 26%, 95%-Ci). Twenty patients had negative skin tests at week 0 and week 4; six were positive both times, and 13 converted their DTH from negative to positive, for a conversion rate of 13 of 33 (39%). Patients who received interferon-γ and/or GM-CSF as an adjuvant had a higher rate of DTH conversion compared to patients who received other adjuvants (13 of 20 v 2 of 13, P = 0.003). For patients who were NED, nine of 19 (47%) converted their DTH test compared to four of 14 (29%) patients with metastatic disease (p = 0.33). For patients whose DTH converted from negative to positive after 3 weeks of vaccination, median FFS and OS were superior compared to patients whose DTH remained negative (19.4 v 4.0 months FFS, p = 0.0052 and 39.6 v 18.3 months OS, p = 0.0602). The autologous cell line approach to active specific immunotherapy is feasible for patients who have resectable foci of metastatic disease. Administration of such patient-specific vaccines improves survival for those patients who are NED at the time of vaccination and convert their DTH skin test, compared to those whose DTH test remains negative.

Original languageEnglish (US)
Pages (from-to)165-176
Number of pages12
JournalCancer Biotherapy and Radiopharmaceuticals
Volume13
Issue number3
DOIs
StatePublished - Jan 1 1998

Fingerprint

Active Immunotherapy
Tumor Cell Line
Melanoma
Survival
Vaccination
Skin Tests
Vaccines
Granulocyte-Macrophage Colony-Stimulating Factor
Interferons
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

Cite this

Clinical experience with autologous tumor cell lines for patient- specific vaccine therapy in metastatic melanoma. / Dillman, Robert O.; Nayak, Shankar K.; Barth, Neil M.; Deleon, Cristina; Schwartzberg, Lee; Spitler, Lynn E.; Church, Curtis; O'Connor, Audrey A.; Beutel, Linda D.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 13, No. 3, 01.01.1998, p. 165-176.

Research output: Contribution to journalArticle

Dillman, Robert O. ; Nayak, Shankar K. ; Barth, Neil M. ; Deleon, Cristina ; Schwartzberg, Lee ; Spitler, Lynn E. ; Church, Curtis ; O'Connor, Audrey A. ; Beutel, Linda D. / Clinical experience with autologous tumor cell lines for patient- specific vaccine therapy in metastatic melanoma. In: Cancer Biotherapy and Radiopharmaceuticals. 1998 ; Vol. 13, No. 3. pp. 165-176.
@article{dbbc3d8153a946b2ab1d3bb9df6dd3c7,
title = "Clinical experience with autologous tumor cell lines for patient- specific vaccine therapy in metastatic melanoma",
abstract = "Because of their patient specificity and proliferative capacity, tumor cell lines established from autologous metastatic melanoma tumor samples may be an excellent immunogen for patient-specific vaccine therapy. Between October 1990 and July 1996, the Hoag Cancer Center cell biology laboratory received 136 fresh metastatic melanoma samples from 122 different patients. Tumor cell lines were successfully established for 92 of 136 samples (68{\%}), for 87 of 122 patients (71{\%}). Successful cultures were expanded to 108 cells (total culture time about 8 weeks), confirmed to be sterile, irradiated, and stored frozen in aliquots of 107 cells. Vaccines were prepared from 72 lines, and 62 vaccines were used in 57 different patients. Subcutaneous vaccination took place on weeks 1, 2 and 3, and then monthly for a total of 6 months. A delayed tumor hypersensitivity skin test (DTH) was administered at week zero and week 4. Various adjuvants were co-administered including BCG, α- or γ-interferon, and GM-CSF. Patients were monitored for failure-free survival (FFS) and overall survival (OS) from the date of the first vaccination. Follow-up data is available for 52 patients, 27 who had no evident disease (NED) at the time of vaccination and 25 who had metastatic disease at the time of treatment. There were two partial responses which persisted 11.9 and 39.8+ months among the 25 patients who had detectable metastatic disease whun treatment was initiated (8{\%}, 1 to 26{\%}, 95{\%}-Ci). Twenty patients had negative skin tests at week 0 and week 4; six were positive both times, and 13 converted their DTH from negative to positive, for a conversion rate of 13 of 33 (39{\%}). Patients who received interferon-γ and/or GM-CSF as an adjuvant had a higher rate of DTH conversion compared to patients who received other adjuvants (13 of 20 v 2 of 13, P = 0.003). For patients who were NED, nine of 19 (47{\%}) converted their DTH test compared to four of 14 (29{\%}) patients with metastatic disease (p = 0.33). For patients whose DTH converted from negative to positive after 3 weeks of vaccination, median FFS and OS were superior compared to patients whose DTH remained negative (19.4 v 4.0 months FFS, p = 0.0052 and 39.6 v 18.3 months OS, p = 0.0602). The autologous cell line approach to active specific immunotherapy is feasible for patients who have resectable foci of metastatic disease. Administration of such patient-specific vaccines improves survival for those patients who are NED at the time of vaccination and convert their DTH skin test, compared to those whose DTH test remains negative.",
author = "Dillman, {Robert O.} and Nayak, {Shankar K.} and Barth, {Neil M.} and Cristina Deleon and Lee Schwartzberg and Spitler, {Lynn E.} and Curtis Church and O'Connor, {Audrey A.} and Beutel, {Linda D.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1089/cbr.1998.13.165",
language = "English (US)",
volume = "13",
pages = "165--176",
journal = "Cancer Biotherapy and Radiopharmaceuticals",
issn = "1084-9785",
publisher = "Mary Ann Liebert Inc.",
number = "3",

}

TY - JOUR

T1 - Clinical experience with autologous tumor cell lines for patient- specific vaccine therapy in metastatic melanoma

AU - Dillman, Robert O.

AU - Nayak, Shankar K.

AU - Barth, Neil M.

AU - Deleon, Cristina

AU - Schwartzberg, Lee

AU - Spitler, Lynn E.

AU - Church, Curtis

AU - O'Connor, Audrey A.

AU - Beutel, Linda D.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Because of their patient specificity and proliferative capacity, tumor cell lines established from autologous metastatic melanoma tumor samples may be an excellent immunogen for patient-specific vaccine therapy. Between October 1990 and July 1996, the Hoag Cancer Center cell biology laboratory received 136 fresh metastatic melanoma samples from 122 different patients. Tumor cell lines were successfully established for 92 of 136 samples (68%), for 87 of 122 patients (71%). Successful cultures were expanded to 108 cells (total culture time about 8 weeks), confirmed to be sterile, irradiated, and stored frozen in aliquots of 107 cells. Vaccines were prepared from 72 lines, and 62 vaccines were used in 57 different patients. Subcutaneous vaccination took place on weeks 1, 2 and 3, and then monthly for a total of 6 months. A delayed tumor hypersensitivity skin test (DTH) was administered at week zero and week 4. Various adjuvants were co-administered including BCG, α- or γ-interferon, and GM-CSF. Patients were monitored for failure-free survival (FFS) and overall survival (OS) from the date of the first vaccination. Follow-up data is available for 52 patients, 27 who had no evident disease (NED) at the time of vaccination and 25 who had metastatic disease at the time of treatment. There were two partial responses which persisted 11.9 and 39.8+ months among the 25 patients who had detectable metastatic disease whun treatment was initiated (8%, 1 to 26%, 95%-Ci). Twenty patients had negative skin tests at week 0 and week 4; six were positive both times, and 13 converted their DTH from negative to positive, for a conversion rate of 13 of 33 (39%). Patients who received interferon-γ and/or GM-CSF as an adjuvant had a higher rate of DTH conversion compared to patients who received other adjuvants (13 of 20 v 2 of 13, P = 0.003). For patients who were NED, nine of 19 (47%) converted their DTH test compared to four of 14 (29%) patients with metastatic disease (p = 0.33). For patients whose DTH converted from negative to positive after 3 weeks of vaccination, median FFS and OS were superior compared to patients whose DTH remained negative (19.4 v 4.0 months FFS, p = 0.0052 and 39.6 v 18.3 months OS, p = 0.0602). The autologous cell line approach to active specific immunotherapy is feasible for patients who have resectable foci of metastatic disease. Administration of such patient-specific vaccines improves survival for those patients who are NED at the time of vaccination and convert their DTH skin test, compared to those whose DTH test remains negative.

AB - Because of their patient specificity and proliferative capacity, tumor cell lines established from autologous metastatic melanoma tumor samples may be an excellent immunogen for patient-specific vaccine therapy. Between October 1990 and July 1996, the Hoag Cancer Center cell biology laboratory received 136 fresh metastatic melanoma samples from 122 different patients. Tumor cell lines were successfully established for 92 of 136 samples (68%), for 87 of 122 patients (71%). Successful cultures were expanded to 108 cells (total culture time about 8 weeks), confirmed to be sterile, irradiated, and stored frozen in aliquots of 107 cells. Vaccines were prepared from 72 lines, and 62 vaccines were used in 57 different patients. Subcutaneous vaccination took place on weeks 1, 2 and 3, and then monthly for a total of 6 months. A delayed tumor hypersensitivity skin test (DTH) was administered at week zero and week 4. Various adjuvants were co-administered including BCG, α- or γ-interferon, and GM-CSF. Patients were monitored for failure-free survival (FFS) and overall survival (OS) from the date of the first vaccination. Follow-up data is available for 52 patients, 27 who had no evident disease (NED) at the time of vaccination and 25 who had metastatic disease at the time of treatment. There were two partial responses which persisted 11.9 and 39.8+ months among the 25 patients who had detectable metastatic disease whun treatment was initiated (8%, 1 to 26%, 95%-Ci). Twenty patients had negative skin tests at week 0 and week 4; six were positive both times, and 13 converted their DTH from negative to positive, for a conversion rate of 13 of 33 (39%). Patients who received interferon-γ and/or GM-CSF as an adjuvant had a higher rate of DTH conversion compared to patients who received other adjuvants (13 of 20 v 2 of 13, P = 0.003). For patients who were NED, nine of 19 (47%) converted their DTH test compared to four of 14 (29%) patients with metastatic disease (p = 0.33). For patients whose DTH converted from negative to positive after 3 weeks of vaccination, median FFS and OS were superior compared to patients whose DTH remained negative (19.4 v 4.0 months FFS, p = 0.0052 and 39.6 v 18.3 months OS, p = 0.0602). The autologous cell line approach to active specific immunotherapy is feasible for patients who have resectable foci of metastatic disease. Administration of such patient-specific vaccines improves survival for those patients who are NED at the time of vaccination and convert their DTH skin test, compared to those whose DTH test remains negative.

UR - http://www.scopus.com/inward/record.url?scp=0031824962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031824962&partnerID=8YFLogxK

U2 - 10.1089/cbr.1998.13.165

DO - 10.1089/cbr.1998.13.165

M3 - Article

C2 - 10850352

AN - SCOPUS:0031824962

VL - 13

SP - 165

EP - 176

JO - Cancer Biotherapy and Radiopharmaceuticals

JF - Cancer Biotherapy and Radiopharmaceuticals

SN - 1084-9785

IS - 3

ER -