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CD4(+) T Cells Play a Critical Role in the Generation of Primary and Memory Antitumor Immune Responses Elicited by SA-4-1BBL and TAA-Based Vaccines in Mouse Tumor Models

The role of CD4(+) T cells in the generation of therapeutic primary and memory immune responses in cancer diverse immunotherapy settings remains ambiguous. We herein investigated this issue using two vaccine formulations containing a novel costimulatory molecule, SA-4-1BBL, as adjuvant and HPV E7 or...

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Autores principales: Sharma, Rajesh K., Yolcu, Esma S., Srivastava, Abhishek K., Shirwan, Haval
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774737/
https://www.ncbi.nlm.nih.gov/pubmed/24066030
http://dx.doi.org/10.1371/journal.pone.0073145
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author Sharma, Rajesh K.
Yolcu, Esma S.
Srivastava, Abhishek K.
Shirwan, Haval
author_facet Sharma, Rajesh K.
Yolcu, Esma S.
Srivastava, Abhishek K.
Shirwan, Haval
author_sort Sharma, Rajesh K.
collection PubMed
description The role of CD4(+) T cells in the generation of therapeutic primary and memory immune responses in cancer diverse immunotherapy settings remains ambiguous. We herein investigated this issue using two vaccine formulations containing a novel costimulatory molecule, SA-4-1BBL, as adjuvant and HPV E7 or survivin (SVN) as tumor associated antigens (TAAs) in two mouse transplantable tumor models; the TC-1 cervical cancer expressing xenogeneic HPV E7 and 3LL lung carcinoma overexpressing autologous SVN. Single vaccination with optimized SA-4-1BBL/TAA formulations resulted in the eradication of 6-day established TC-1 and 3LL tumors in >70% of mice in both models. The in vivo depletion of CD4(+) T cells one day before tumor challenge resulted in compromised vaccine efficacy in both TC-1 (25%) and 3LL (12.5%) tumor models. In marked contrast, depletion of CD4(+) T cells 5 days post-tumor challenge and one day prior to vaccination did not significantly alter the therapeutic efficacy of these vaccines. However, long-term immunological memory was compromised in the 3LL, but not in TC-1 model as a significant number (85.7%) of tumor free-mice succumbed to tumor growth when rechallenged with 3LL cells 60 days after the initial tumor inoculation. Collectively, these results demonstrate the indispensable role CD4(+) T cells play in the generation of therapeutic primary immune responses elicited by SA-4-1BBL/TAA-based vaccines irrespective of the nature of TAAs and establish the importance of CD4(+) T cells for long-term immune memory against 3LL tumor expressing self-antigen SVN, but not TC-1 expressing xenogeneic viral antigen E7.
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spelling pubmed-37747372013-09-24 CD4(+) T Cells Play a Critical Role in the Generation of Primary and Memory Antitumor Immune Responses Elicited by SA-4-1BBL and TAA-Based Vaccines in Mouse Tumor Models Sharma, Rajesh K. Yolcu, Esma S. Srivastava, Abhishek K. Shirwan, Haval PLoS One Research Article The role of CD4(+) T cells in the generation of therapeutic primary and memory immune responses in cancer diverse immunotherapy settings remains ambiguous. We herein investigated this issue using two vaccine formulations containing a novel costimulatory molecule, SA-4-1BBL, as adjuvant and HPV E7 or survivin (SVN) as tumor associated antigens (TAAs) in two mouse transplantable tumor models; the TC-1 cervical cancer expressing xenogeneic HPV E7 and 3LL lung carcinoma overexpressing autologous SVN. Single vaccination with optimized SA-4-1BBL/TAA formulations resulted in the eradication of 6-day established TC-1 and 3LL tumors in >70% of mice in both models. The in vivo depletion of CD4(+) T cells one day before tumor challenge resulted in compromised vaccine efficacy in both TC-1 (25%) and 3LL (12.5%) tumor models. In marked contrast, depletion of CD4(+) T cells 5 days post-tumor challenge and one day prior to vaccination did not significantly alter the therapeutic efficacy of these vaccines. However, long-term immunological memory was compromised in the 3LL, but not in TC-1 model as a significant number (85.7%) of tumor free-mice succumbed to tumor growth when rechallenged with 3LL cells 60 days after the initial tumor inoculation. Collectively, these results demonstrate the indispensable role CD4(+) T cells play in the generation of therapeutic primary immune responses elicited by SA-4-1BBL/TAA-based vaccines irrespective of the nature of TAAs and establish the importance of CD4(+) T cells for long-term immune memory against 3LL tumor expressing self-antigen SVN, but not TC-1 expressing xenogeneic viral antigen E7. Public Library of Science 2013-09-16 /pmc/articles/PMC3774737/ /pubmed/24066030 http://dx.doi.org/10.1371/journal.pone.0073145 Text en © 2013 Sharma et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sharma, Rajesh K.
Yolcu, Esma S.
Srivastava, Abhishek K.
Shirwan, Haval
CD4(+) T Cells Play a Critical Role in the Generation of Primary and Memory Antitumor Immune Responses Elicited by SA-4-1BBL and TAA-Based Vaccines in Mouse Tumor Models
title CD4(+) T Cells Play a Critical Role in the Generation of Primary and Memory Antitumor Immune Responses Elicited by SA-4-1BBL and TAA-Based Vaccines in Mouse Tumor Models
title_full CD4(+) T Cells Play a Critical Role in the Generation of Primary and Memory Antitumor Immune Responses Elicited by SA-4-1BBL and TAA-Based Vaccines in Mouse Tumor Models
title_fullStr CD4(+) T Cells Play a Critical Role in the Generation of Primary and Memory Antitumor Immune Responses Elicited by SA-4-1BBL and TAA-Based Vaccines in Mouse Tumor Models
title_full_unstemmed CD4(+) T Cells Play a Critical Role in the Generation of Primary and Memory Antitumor Immune Responses Elicited by SA-4-1BBL and TAA-Based Vaccines in Mouse Tumor Models
title_short CD4(+) T Cells Play a Critical Role in the Generation of Primary and Memory Antitumor Immune Responses Elicited by SA-4-1BBL and TAA-Based Vaccines in Mouse Tumor Models
title_sort cd4(+) t cells play a critical role in the generation of primary and memory antitumor immune responses elicited by sa-4-1bbl and taa-based vaccines in mouse tumor models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774737/
https://www.ncbi.nlm.nih.gov/pubmed/24066030
http://dx.doi.org/10.1371/journal.pone.0073145
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