Autologous dendritic cell based adoptive immunotherapy of patients with colorectal cancer - A phase i-ii study

J. Hunyadi, C. András, Imre Szabó, J. Szántó, Kornélia Szluha, S. Sipka, Péter Kovács, Attila Kiss, G. Szegedi, I. Altorjay, P. Sápy, P. Antal-Szalmás, L. Tóth, György Fazekas, E. Rajnavolgyi

Research output: Article

13 Citations (Scopus)

Abstract

Dendritic cell-based active immunotherapies of cancer patients are aimed to provoke the proliferation and differentiation of tumor-specific CD4+ and CD8+ T-lymphocytes towards protective effector cells. Isolation and in vitro differentiation of circulating blood monocytes has been established a reasonable platform for adoptively transferred DC-based immunotherapies. In the present study the safety and tolerability of vaccination by autologous tumor cell lysates (oncolysate)- or carcinoembriogenic antigen (CEA)-loaded DCs in patients with colorectal cancer was investigated in a phase I-II trial. The study included 12 patients with histologically confirmed colorectal cancer (Dukes B2-C stages). Six of the patients received oncolysate-pulsed, whereas the other six received recombinant CEA-loaded autologous DCs. The potential of the tumor antigen-loaded DCs to provoke the patient's immune system was studied both in vivo and in vitro. The clinical outcome of the therapy evaluated after 7 years revealed that none of the six patients treated with oncolysate-loaded DCs showed relapse of colorectal cancer, whereas three out of the six patients treated with CEA-loaded DCs died because of tumor relapse. Immunization with both the oncolysate- and the CEA-loaded autologous DCs induced measurable immune responses, which could be detected in vivo by cutaneous reactions and in vitro by lymphocyte proliferation assay. Our results show that vaccination by autologous DCs loaded with autologous oncolysates containing various tumor antigens represents a well tolerated therapeutic modality in patients with colorectal cancer without any detectable adverse effects. Demonstration of the efficacy of such therapy needs further studies with increased number of patients.

Original languageEnglish
Pages (from-to)357-365
Number of pages9
JournalPathology and Oncology Research
Volume20
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Adoptive Immunotherapy
Dendritic Cells
Colorectal Neoplasms
Autoantigens
Neoplasm Antigens
Neoplasms
Vaccination
Antigens
Active Immunotherapy
Recurrence
Immunotherapy
Monocytes
Immune System
Immunization
Therapeutics
Lymphocytes
T-Lymphocytes
Safety
Skin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

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title = "Autologous dendritic cell based adoptive immunotherapy of patients with colorectal cancer - A phase i-ii study",
abstract = "Dendritic cell-based active immunotherapies of cancer patients are aimed to provoke the proliferation and differentiation of tumor-specific CD4+ and CD8+ T-lymphocytes towards protective effector cells. Isolation and in vitro differentiation of circulating blood monocytes has been established a reasonable platform for adoptively transferred DC-based immunotherapies. In the present study the safety and tolerability of vaccination by autologous tumor cell lysates (oncolysate)- or carcinoembriogenic antigen (CEA)-loaded DCs in patients with colorectal cancer was investigated in a phase I-II trial. The study included 12 patients with histologically confirmed colorectal cancer (Dukes B2-C stages). Six of the patients received oncolysate-pulsed, whereas the other six received recombinant CEA-loaded autologous DCs. The potential of the tumor antigen-loaded DCs to provoke the patient's immune system was studied both in vivo and in vitro. The clinical outcome of the therapy evaluated after 7 years revealed that none of the six patients treated with oncolysate-loaded DCs showed relapse of colorectal cancer, whereas three out of the six patients treated with CEA-loaded DCs died because of tumor relapse. Immunization with both the oncolysate- and the CEA-loaded autologous DCs induced measurable immune responses, which could be detected in vivo by cutaneous reactions and in vitro by lymphocyte proliferation assay. Our results show that vaccination by autologous DCs loaded with autologous oncolysates containing various tumor antigens represents a well tolerated therapeutic modality in patients with colorectal cancer without any detectable adverse effects. Demonstration of the efficacy of such therapy needs further studies with increased number of patients.",
keywords = "Autologous, Colorectal cancer, Dendritic cell, Vaccination",
author = "J. Hunyadi and C. Andr{\'a}s and Imre Szab{\'o} and J. Sz{\'a}nt{\'o} and Korn{\'e}lia Szluha and S. Sipka and P{\'e}ter Kov{\'a}cs and Attila Kiss and G. Szegedi and I. Altorjay and P. S{\'a}py and P. Antal-Szalm{\'a}s and L. T{\'o}th and Gy{\"o}rgy Fazekas and E. Rajnavolgyi",
year = "2014",
doi = "10.1007/s12253-013-9704-3",
language = "English",
volume = "20",
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T1 - Autologous dendritic cell based adoptive immunotherapy of patients with colorectal cancer - A phase i-ii study

AU - Hunyadi, J.

AU - András, C.

AU - Szabó, Imre

AU - Szántó, J.

AU - Szluha, Kornélia

AU - Sipka, S.

AU - Kovács, Péter

AU - Kiss, Attila

AU - Szegedi, G.

AU - Altorjay, I.

AU - Sápy, P.

AU - Antal-Szalmás, P.

AU - Tóth, L.

AU - Fazekas, György

AU - Rajnavolgyi, E.

PY - 2014

Y1 - 2014

N2 - Dendritic cell-based active immunotherapies of cancer patients are aimed to provoke the proliferation and differentiation of tumor-specific CD4+ and CD8+ T-lymphocytes towards protective effector cells. Isolation and in vitro differentiation of circulating blood monocytes has been established a reasonable platform for adoptively transferred DC-based immunotherapies. In the present study the safety and tolerability of vaccination by autologous tumor cell lysates (oncolysate)- or carcinoembriogenic antigen (CEA)-loaded DCs in patients with colorectal cancer was investigated in a phase I-II trial. The study included 12 patients with histologically confirmed colorectal cancer (Dukes B2-C stages). Six of the patients received oncolysate-pulsed, whereas the other six received recombinant CEA-loaded autologous DCs. The potential of the tumor antigen-loaded DCs to provoke the patient's immune system was studied both in vivo and in vitro. The clinical outcome of the therapy evaluated after 7 years revealed that none of the six patients treated with oncolysate-loaded DCs showed relapse of colorectal cancer, whereas three out of the six patients treated with CEA-loaded DCs died because of tumor relapse. Immunization with both the oncolysate- and the CEA-loaded autologous DCs induced measurable immune responses, which could be detected in vivo by cutaneous reactions and in vitro by lymphocyte proliferation assay. Our results show that vaccination by autologous DCs loaded with autologous oncolysates containing various tumor antigens represents a well tolerated therapeutic modality in patients with colorectal cancer without any detectable adverse effects. Demonstration of the efficacy of such therapy needs further studies with increased number of patients.

AB - Dendritic cell-based active immunotherapies of cancer patients are aimed to provoke the proliferation and differentiation of tumor-specific CD4+ and CD8+ T-lymphocytes towards protective effector cells. Isolation and in vitro differentiation of circulating blood monocytes has been established a reasonable platform for adoptively transferred DC-based immunotherapies. In the present study the safety and tolerability of vaccination by autologous tumor cell lysates (oncolysate)- or carcinoembriogenic antigen (CEA)-loaded DCs in patients with colorectal cancer was investigated in a phase I-II trial. The study included 12 patients with histologically confirmed colorectal cancer (Dukes B2-C stages). Six of the patients received oncolysate-pulsed, whereas the other six received recombinant CEA-loaded autologous DCs. The potential of the tumor antigen-loaded DCs to provoke the patient's immune system was studied both in vivo and in vitro. The clinical outcome of the therapy evaluated after 7 years revealed that none of the six patients treated with oncolysate-loaded DCs showed relapse of colorectal cancer, whereas three out of the six patients treated with CEA-loaded DCs died because of tumor relapse. Immunization with both the oncolysate- and the CEA-loaded autologous DCs induced measurable immune responses, which could be detected in vivo by cutaneous reactions and in vitro by lymphocyte proliferation assay. Our results show that vaccination by autologous DCs loaded with autologous oncolysates containing various tumor antigens represents a well tolerated therapeutic modality in patients with colorectal cancer without any detectable adverse effects. Demonstration of the efficacy of such therapy needs further studies with increased number of patients.

KW - Autologous

KW - Colorectal cancer

KW - Dendritic cell

KW - Vaccination

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U2 - 10.1007/s12253-013-9704-3

DO - 10.1007/s12253-013-9704-3

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VL - 20

SP - 357

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JO - Pathology and Oncology Research

JF - Pathology and Oncology Research

SN - 1219-4956

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