Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma

Maurizio Bendandi, Christopher Gocke, Carol Kobrin, Floyd A. Benko, Lars A. Sternas, Robin Pennington, Thelma M. Watson, Craig W. Reynolds, Barry L. Gause, Patricia L. Duffey, Elaine S. Jaffe, Stephen P. Creekmore, Dan L. Longo, Larry W. Kwak

Research output: Contribution to journalArticle

Abstract

Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.

Original languageEnglish (US)
Pages (from-to)1171-1177
Number of pages7
JournalNature Medicine
Volume5
Issue number10
DOIs
StatePublished - Oct 1999
Externally publishedYes

Fingerprint

Colony-Stimulating Factors
Granulocyte Colony-Stimulating Factor
Tumors
Monocytes
Lymphoma
Vaccination
Residual Neoplasm
Blood
Chemotherapy
T-cells
Neoplasms
Vaccines
Clone Cells
Drug Therapy
Polymerase Chain Reaction
Cancer Vaccines
Cytotoxic T-Lymphocytes
Neoplasm Antigens
Disease-Free Survival
Blood Cells

ASJC Scopus subject areas

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

Cite this

Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. / Bendandi, Maurizio; Gocke, Christopher; Kobrin, Carol; Benko, Floyd A.; Sternas, Lars A.; Pennington, Robin; Watson, Thelma M.; Reynolds, Craig W.; Gause, Barry L.; Duffey, Patricia L.; Jaffe, Elaine S.; Creekmore, Stephen P.; Longo, Dan L.; Kwak, Larry W.

In: Nature Medicine, Vol. 5, No. 10, 10.1999, p. 1171-1177.

Research output: Contribution to journalArticle

Bendandi, M, Gocke, C, Kobrin, C, Benko, FA, Sternas, LA, Pennington, R, Watson, TM, Reynolds, CW, Gause, BL, Duffey, PL, Jaffe, ES, Creekmore, SP, Longo, DL & Kwak, LW 1999, 'Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma', Nature Medicine, vol. 5, no. 10, pp. 1171-1177. https://doi.org/10.1038/13928
Bendandi, Maurizio ; Gocke, Christopher ; Kobrin, Carol ; Benko, Floyd A. ; Sternas, Lars A. ; Pennington, Robin ; Watson, Thelma M. ; Reynolds, Craig W. ; Gause, Barry L. ; Duffey, Patricia L. ; Jaffe, Elaine S. ; Creekmore, Stephen P. ; Longo, Dan L. ; Kwak, Larry W. / Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. In: Nature Medicine. 1999 ; Vol. 5, No. 10. pp. 1171-1177.
@article{c7d9fb503e2b43f2a3d703b7ecaf7cbd,
title = "Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma",
abstract = "Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.",
author = "Maurizio Bendandi and Christopher Gocke and Carol Kobrin and Benko, {Floyd A.} and Sternas, {Lars A.} and Robin Pennington and Watson, {Thelma M.} and Reynolds, {Craig W.} and Gause, {Barry L.} and Duffey, {Patricia L.} and Jaffe, {Elaine S.} and Creekmore, {Stephen P.} and Longo, {Dan L.} and Kwak, {Larry W.}",
year = "1999",
month = "10",
doi = "10.1038/13928",
language = "English (US)",
volume = "5",
pages = "1171--1177",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma

AU - Bendandi, Maurizio

AU - Gocke, Christopher

AU - Kobrin, Carol

AU - Benko, Floyd A.

AU - Sternas, Lars A.

AU - Pennington, Robin

AU - Watson, Thelma M.

AU - Reynolds, Craig W.

AU - Gause, Barry L.

AU - Duffey, Patricia L.

AU - Jaffe, Elaine S.

AU - Creekmore, Stephen P.

AU - Longo, Dan L.

AU - Kwak, Larry W.

PY - 1999/10

Y1 - 1999/10

N2 - Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.

AB - Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.

UR - http://www.scopus.com/inward/record.url?scp=0032828653&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032828653&partnerID=8YFLogxK

U2 - 10.1038/13928

DO - 10.1038/13928

M3 - Article

C2 - 10502821

AN - SCOPUS:0032828653

VL - 5

SP - 1171

EP - 1177

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 10

ER -