Yangbing Zhao, Maria R. Parkhurst, Zhili Zheng, Cyrille J. Cohen, John P. Riley, Luca Gattinoni, ...
Adoptive cell transfer (ACT) of tumor-reactive lymphocytes has been shown to be an effective treatment for cancer patients. Studies in murine models of ACT indicated that antitumor efficacy of...
TSCOT + Thymic Epithelial Cell-Mediated Sensitive CD4 Tolerance by Direct Presentation (2008)
Sejin Ahn, Gwanghee Lee, Soo Jung Yang, Deokjae Lee, Seunghyuk Lee, Hyo Sun Shin, ...
Although much effort has been directed at dissecting the mechanisms of central tolerance, the role of thymic stromal cells remains elusive. In order to further characterize this event, we developed a...
Neeley, Yilin C., McDonagh, Kevin T., Overwijk, Willem W., Restifo, Nicholas P., Sanda, Martin G.
BACKGROUND Cancers can escape immune recognition by means of evading class I major histocompatibility complex (MHC) -mediated recognition by cytotoxic T lymphocytes. However, immunization strategies...
Sanda, Martin G., Charles, Linda G., Xie, Yilin C., Roessler, Blake J., Restifo, Nicholas P.
One potential use for prostate-cancer-associated genes discovered through ongoing genetics studies entails the construction of virus- or plasmid-based recombinant vector vaccines encoding these new...
Restifo, Nicholas P., Marincola, Francesco M., Kawakami, Yutaka, Taubenberger, Jeff, Yannelli, John R., Rosenberg, Steven A.
Background: In a subset of patients with metastatic melanoma, T lymphocytes bearing the cell-surface marker CD8 (CD8+ T cells) can cause the regression of even large tumors. These antitumor...
Molecular Characterization of Defective Antigen Processing in Human Prostate Cancer (1995)
Sanda, Martin G., Restifo, Nicholas P., Walsh, Jonathan C., Kawakami, Yutaka, Nelson, William G., Pardoll, Drew M., ...
Background:Gene-modified tumor cell vaccines have shown efficacy in animal models of malignancy, including prostate cancer. Class I major histocompatibility complex (MHC) assembly and function in the...
Overwijk, Willem W., Lee, David S., Surman, Deborah R., Irvine, Kari R., Touloukian, Christopher E., Chan, Chi-Chao, ...
Many human and mouse tumor antigens are normal, nonmutated tissue differentiation antigens. Consequently, immunization with these “self” antigens could induce autoimmunity. When we tried to...
Bronte, Vincenzo, Carroll, Miles W., Goletz, Theresa J., Wang, Michael, Overwijk, Willem W., Marincola, Francesco, ...
Recombinant poxviruses encoding tumor-associated antigens (TAA) are attractive as candidate cancer vaccines. Their effectiveness, however, will depend upon expression of the TAA in appropriate...
Porgador, Angel, Mandelboim, Ofer, Restifo, Nicholas P., Strominger, Jack L.
Cancer vaccines used to generate specific cytotoxic T lymphocytes are not effective against tumor cells that have lost or suppressed expression of their class I major histocompatibility complex...
An autologous oral DNA vaccine protects against murine melanoma
Xiang, Rong, Lode, Holger N., Chao, Ta-Hsiang, Ruehlmann, J. Michael, Dolman, Carrie S., Rodriguez, Fernando, ...
We demonstrated that peripheral T cell tolerance toward murine melanoma self-antigens gp100 and TRP-2 can be broken by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to...
Wang, Helen Y., Fu, Tihui, Wang, Gang, Zeng, Gang, Perry-Lalley, Donna M., Yang, James C., ...
Dendritic cell–based (DC-based) immunotherapy represents a promising approach to the prevention and treatment of many diseases, including cancer, but current strategies have met with only limited...
DNA vaccines and apoptosis: to kill or not to kill?
Leitner, Wolfgang W., Restifo, Nicholas P.
The apoptotic machinery has become the latest target of vaccinologists attempting to improve the efficacy of DNA vaccines. While workers have previously sought to induce apoptotic death in...
Phan, Giao Q., Yang, James C., Sherry, Richard M., Hwu, Patrick, Topalian, Suzanne L., Schwartzentruber, Douglas J., ...
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell...
IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T Cells
Klebanoff, Christopher A., Finkelstein, Steven E., Surman, Deborah R., Lichtman, Michael K., Gattinoni, Luca, Theoret, Marc R., ...
IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8+ memory T cell survival and proliferation,...
Yu, Zhiya, Theoret, Marc R., Touloukian, Christopher E., Surman, Deborah R., Garman, Scott C., Feigenbaum, Lionel, ...
Understanding the mechanisms underlying the poor immunogenicity of human self/tumor antigens is challenging because of experimental limitations in humans. Here, we developed a human-mouse chimeric...
Gattinoni, Luca, Klebanoff, Christopher A., Palmer, Douglas C., Wrzesinski, Claudia, Kerstann, Keith, Yu, Zhiya, ...
T cell differentiation is a progressive process characterized by phenotypic and functional changes. By transferring tumor-specific CD8+ T cells into tumor-bearing mice at various stages of...
Klebanoff, Christopher A., Gattinoni, Luca, Torabi-Parizi, Parizad, Kerstann, Keith, Cardones, Adela R., Finkelstein, Steven E., ...
Central memory CD8+ T cells (TCM) and effector memory CD8+ T cells (TEM) are found in humans and mice; however, their relative contributions to host immunity have only recently been examined in vivo....
Wrzesinski, Claudia, Restifo, Nicholas P
Adoptive T-cell immunotherapy combined with non-myeloablative lymphodepletion has emerged as the most effective immunotherapy treatment for patients with metastatic melanoma (objective response rates...
Klebanoff, Christopher A, Khong, Hung T, Antony, Paul A, Palmer, Douglas C, Restifo, Nicholas P
Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials,...
Gattinoni, Luca, Finkelstein, Steven E., Klebanoff, Christopher A., Antony, Paul A., Palmer, Douglas C., Spiess, Paul J., ...
Depletion of immune elements before adoptive cell transfer (ACT) can dramatically improve the antitumor efficacy of transferred CD8+ T cells, but the specific mechanisms that contribute to this...
Antony, Paul A., Piccirillo, Ciriaco A., Akpinarli, Akgül, Finkelstein, Steven E., Speiss, Paul J., Surman, Deborah R., ...
CD4+ T cells control the effector function, memory, and maintenance of CD8+ T cells. Paradoxically, we found that absence of CD4+ T cells enhanced adoptive immunotherapy of cancer when using CD8+ T...
Cancer immunotherapy: moving beyond current vaccines
Rosenberg, Steven A, Yang, James C, Restifo, Nicholas P
Great progress has been made in the field of tumor immunology in the past decade, but optimism about the clinical application of currently available cancer vaccine approaches is based more on...
Do CD4+CD25+ Immunoregulatory T Cells Hinder Tumor Immunotherapy?
Antony, Paul Andrew, Restifo, Nicholas P.
After years of banishment from mainstream immunology, the notion that one subset of T cells can exert regulatory effects on other T lymphocytes is back in fashion. Recent work in knockout and...
Adoptive immunotherapy for cancer: building on success
Gattinoni, Luca, Powell, Daniel J., Rosenberg, Steven A., Restifo, Nicholas P.
Adoptive cell transfer after host preconditioning by lymphodepletion represents an important advance in cancer immunotherapy. Here, we describe how a lymphopaenic environment enables tumour-reactive...
Interleukin-2-Dependent Mechanisms of Tolerance and Immunity In Vivo1
Antony, Paul A., Paulos, Chrystal M., Ahmadzadeh, Mojgan, Akpinarli, Akgül, Palmer, Douglas C., Sato, Noriko, ...
IL-2 is a critical T cell growth factor in vitro, but predominantly mediates tolerance in vivo. IL-2 is mainly produced by CD4+ Th cells, but the role of Th cell-derived IL-2 in vivo is...
Overwijk, Willem W., Lee, David S., Surman, Deborah R., Irvine, Kari R., Touloukian, Christopher E., Chan, Chi-Chao, ...
Many human and mouse tumor antigens are normal, nonmutated tissue differentiation antigens. Consequently, immunization with these “self” antigens could induce autoimmunity. When we tried to...
Bronte, Vincenzo, Carroll, Miles W., Goletz, Theresa J., Wang, Michael, Overwijk, Willem W., Marincola, Francesco, ...
Recombinant poxviruses encoding tumor-associated antigens (TAA) are attractive as candidate cancer vaccines. Their effectiveness, however, will depend upon expression of the TAA in appropriate...
Porgador, Angel, Mandelboim, Ofer, Restifo, Nicholas P., Strominger, Jack L.
Cancer vaccines used to generate specific cytotoxic T lymphocytes are not effective against tumor cells that have lost or suppressed expression of their class I major histocompatibility complex...
An autologous oral DNA vaccine protects against murine melanoma
Xiang, Rong, Lode, Holger N., Chao, Ta-Hsiang, Ruehlmann, J. Michael, Dolman, Carrie S., Rodriguez, Fernando, ...
We demonstrated that peripheral T cell tolerance toward murine melanoma self-antigens gp100 and TRP-2 can be broken by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to...
Wang, Helen Y., Fu, Tihui, Wang, Gang, Zeng, Gang, Perry-Lalley, Donna M., Yang, James C., ...
Dendritic cell–based (DC-based) immunotherapy represents a promising approach to the prevention and treatment of many diseases, including cancer, but current strategies have met with only limited...
DNA vaccines and apoptosis: to kill or not to kill?
Leitner, Wolfgang W., Restifo, Nicholas P.
The apoptotic machinery has become the latest target of vaccinologists attempting to improve the efficacy of DNA vaccines. While workers have previously sought to induce apoptotic death in...
Phan, Giao Q., Yang, James C., Sherry, Richard M., Hwu, Patrick, Topalian, Suzanne L., Schwartzentruber, Douglas J., ...
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell...
IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T Cells
Klebanoff, Christopher A., Finkelstein, Steven E., Surman, Deborah R., Lichtman, Michael K., Gattinoni, Luca, Theoret, Marc R., ...
IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8+ memory T cell survival and proliferation,...
Yu, Zhiya, Theoret, Marc R., Touloukian, Christopher E., Surman, Deborah R., Garman, Scott C., Feigenbaum, Lionel, ...
Understanding the mechanisms underlying the poor immunogenicity of human self/tumor antigens is challenging because of experimental limitations in humans. Here, we developed a human-mouse chimeric...
Gattinoni, Luca, Klebanoff, Christopher A., Palmer, Douglas C., Wrzesinski, Claudia, Kerstann, Keith, Yu, Zhiya, ...
T cell differentiation is a progressive process characterized by phenotypic and functional changes. By transferring tumor-specific CD8+ T cells into tumor-bearing mice at various stages of...
Klebanoff, Christopher A., Gattinoni, Luca, Torabi-Parizi, Parizad, Kerstann, Keith, Cardones, Adela R., Finkelstein, Steven E., ...
Central memory CD8+ T cells (TCM) and effector memory CD8+ T cells (TEM) are found in humans and mice; however, their relative contributions to host immunity have only recently been examined in vivo....
Wrzesinski, Claudia, Paulos, Chrystal M., Gattinoni, Luca, Palmer, Douglas C., Kaiser, Andrew, Yu, Zhiya, ...
Depleting host immune elements with nonmyeloablative regimens prior to the adoptive transfer of tumor-specific CD8+ T cells significantly enhances tumor treatment. In the current study, superior...
Paulos, Chrystal M., Wrzesinski, Claudia, Hinrichs, Christian S., Chieppa, Marcello, Cassard, Lydie, ...
Lymphodepletion with total body irradiation (TBI) increases the efficacy of adoptively transferred tumor-specific CD8+ T cells by depleting inhibitory lymphocytes and increasing homeostatic cytokine...
Cross-priming utilizes antigen not available to the direct presentation pathway
Donohue, Keri B, Grant, Jean M, Tewalt, Eric F, Palmer, Douglas C, Theoret, Marc R, Restifo, Nicholas P, ...
CD8+ T cells play a crucial role in protective immunity to viruses and tumours. Antiviral CD8+ T cells are initially activated by professional antigen presenting cells (pAPCs) that are directly...
Paulos, Chrystal M., Wrzesinski, Claudia, Kaiser, Andrew, Hinrichs, Christian S., Chieppa, Marcello, Cassard, Lydie, ...
CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent
Gattinoni, Luca, Ranganathan, Anju, Surman, Deborah R., Palmer, Douglas C., Antony, Paul A., Theoret, Marc R., ...
Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) maintains peripheral tolerance by suppressing T-cell activation and proliferation but its precise role in vivo remains unclear. We sought to...
Gattinoni, Luca, Finkelstein, Steven E., Klebanoff, Christopher A., Antony, Paul A., Palmer, Douglas C., Spiess, Paul J., ...
Depletion of immune elements before adoptive cell transfer (ACT) can dramatically improve the antitumor efficacy of transferred CD8+ T cells, but the specific mechanisms that contribute to this...
Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function
Zeng, Rong, Spolski, Rosanne, Finkelstein, Steven E., Oh, SangKon, Kovanen, Panu E., Hinrichs, Christian S., ...
Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor γ chain (γc), which is mutated in humans with X-linked severe combined immunodeficiency....
Overwijk, Willem W., Theoret, Marc R., Finkelstein, Steven E., Surman, Deborah R., De Jong, Laurina A., Vyth-Dreese, Florry A., ...
Many tumor-associated antigens are derived from nonmutated “self” proteins. T cells infiltrating tumor deposits recognize self-antigens presented by tumor cells and can be expanded in vivo with...
Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10
Murakami, Takashi, Cardones, Adela R., Finkelstein, Steven E., Restifo, Nicholas P., Klaunberg, Brenda A., Nestle, Frank O., ...
Human melanoma cells frequently express CC chemokine receptor (CCR)10, a receptor whose ligand (CCL27) is constitutively produced by keratinocytes. Compared with B16 murine melanoma, cells rendered...
Colella, Teresa A., Bullock, Timothy N.J., Russell, Liane B., Mullins, David W., Overwijk, Willem W., Luckey, Chance John, ...
The human tyrosinase-derived peptide YMDGTMSQV is presented on the surface of human histocompatibility leukocyte antigen (HLA)-A*0201+ melanomas and has been suggested to be a tumor antigen despite...
Van Elsas, Andrea, Sutmuller, Roger P.M., Hurwitz, Arthur A., Ziskin, Jennifer, Villasenor, Jennifer, Medema, Jan-Paul, ...
We have previously shown that small B16 melanomas can be successfully treated using a combination of anti–cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibody with a granulocyte/macrophage...
Overwijk, Willem W., Tsung, Allan, Irvine, Kari R., Parkhurst, Maria R., Goletz, Theresa J., Tsung, Kangla, ...
Many tumor-associated antigens are nonmutated, poorly immunogenic tissue differentiation antigens. Their weak immunogenicity may be due to “self”-tolerance. To induce autoreactive T cells, we...
Porgador, Angel, Irvine, Kari R., Iwasaki, Akiko, Barber, Brian H., Restifo, Nicholas P., Germain, Ronald N.
Cutaneous gene (DNA) bombardment results in substantial expression of the encoded antigen in the epidermal layer as well as detectable expression in dendritic cells (DC) in draining lymph nodes...
TSCOT + Thymic Epithelial Cell-Mediated Sensitive CD4 Tolerance by Direct Presentation
Ahn, Sejin, Lee, Gwanghee, Yang, Soo Jung, Lee, Deokjae, Lee, Seunghyuk, Shin, Hyo Sun, ...
Although much effort has been directed at dissecting the mechanisms of central tolerance, the role of thymic stromal cells remains elusive. In order to further characterize this event, we developed a...
Palmer, Douglas C., Chan, Chi-Chao, Gattinoni, Luca, Wrzesinski, Claudia, Paulos, Chrystal M., Hinrichs, Christian S., ...
Nonmutated tissue differentiation antigens expressed by tumors are attractive targets for cancer immunotherapy, but the consequences of a highly effective antitumor immune response on self-tissue...
Viral Sequestration of Antigen Subverts Cross Presentation to CD8+ T Cells
Tewalt, Eric F., Grant, Jean M., Granger, Erica L., Palmer, Douglas C., Heuss, Neal D., Gregerson, Dale S., ...
Virus-specific CD8+ T cells (TCD8+) are initially triggered by peptide-MHC Class I complexes on the surface of professional antigen presenting cells (pAPC). Peptide-MHC complexes are produced by two...
IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy
Hinrichs, Christian S., Spolski, Rosanne, Paulos, Chrystal M., Gattinoni, Luca, Kerstann, Keith W., Palmer, Douglas C., ...
IL-2 and IL-21 are closely related cytokines that might have arisen by gene duplication. Both cytokines promote the function of effector CD8+ T cells, but their distinct effects on antigen-driven...
Tumor-specific Th17-polarized cells eradicate large established melanoma
Muranski, Pawel, Boni, Andrea, Antony, Paul A., Cassard, Lydie, Irvine, Kari R., Kaiser, Andrew, ...
CD4+ T cells can differentiate into multiple effector subsets, but the potential roles of these subsets in anti-tumor immunity have not been fully explored. Seeking to study the impact of CD4+ T cell...