scholarly journals An NKT-mediated autologous vaccine generates CD4 T-cell–dependent potent antilymphoma immunity

Blood ◽  
2007 ◽  
Vol 110 (6) ◽  
pp. 2013-2019 ◽  
Author(s):  
Yeonseok Chung ◽  
Hong Qin ◽  
Chang-Yuil Kang ◽  
Sanghee Kim ◽  
Larry W. Kwak ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Antitumor Immunity ◽  
Tumor Antigens ◽  
Tumor Regression ◽  
Vaccination Strategy ◽  
Nkt Cells ◽  
Patient Specific ◽  
Specific Tumor ◽  
Single Vaccination

Abstract Relapses occurring in most patients with lymphoma after antibody or chemotherapy highlight a need for effective vaccination approaches. Autologous tumors are ideal sources of patient-specific tumor antigens for vaccines; however, their poor immunogenicity has been a major obstacle in practice. Natural killer T (NKT) cells have recently emerged as crucial regulators of autoimmunity and tumor immunosurveillance. Here, we show that an autologous lymphoma vaccine that activates NKT cells generated tumor-specific protective immunity in experimental mice. Single vaccination with α-galactosylceramide (αGC)-loaded A20 lymphoma cells elicited effective antitumor immunity against tumor challenge. This vaccination strategy also induced significant tumor regression in A20-bearing mice. Importantly, the survivors from primary tumor inoculation were all resistant to tumor rechallenge, indicative of established adaptive memory immunity. Depletion as well as adoptive transfer studies revealed an exclusive role of conventional CD4+ but not CD8+ T cells in mediating antitumor immunity. In addition, we found normal hematopoietic compartments in the vaccinated mice. Therefore, NKT ligand-loaded lymphoma elicits long-lasting and effective antitumor immunity, which can be further developed as patient- and tumor-specific immunotherapy against human lymphomas.

scholarly journals Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells

2005 ◽  
Vol 202 (11) ◽  
pp. 1507-1516 ◽  
Author(s):  
Kang Liu ◽  
Juliana Idoyaga ◽  
Anna Charalambous ◽  
Shin-ichiro Fujii ◽  
Anthony Bonito ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Nkt Cells ◽  
Patient Specific ◽  
Tumor Resistance ◽  
Adaptive Resistance ◽  
Single Vaccination ◽  
Specific Array

If irradiated tumor cells could be rendered immunogenic, they would provide a safe, broad, and patient-specific array of antigens for immunotherapies. Prior approaches have emphasized genetic transduction of live tumor cells to express cytokines, costimulators, and surrogate foreign antigens. We asked if immunity could be achieved by delivering irradiated, major histocompatibility complex–negative plasmacytoma cells to maturing mouse dendritic cells (DCs) within lymphoid organs. Tumor cells injected intravenously (i.v.) were captured by splenic DCs, whereas subcutaneous (s.c.) injection led only to weak uptake in lymph node or spleen. The natural killer T (NKT) cells mobilizing glycolipid α-galactosyl ceramide, used to mature splenic DCs, served as an effective adjuvant to induce protective immunity. This adjuvant function was mimicked by a combination of poly IC and agonistic αCD40 antibody. The adjuvant glycolipid had to be coadministered with tumor cells i.v. rather than s.c. Specific resistance was generated both to a plasmacytoma and lymphoma. The resistance afforded by a single vaccination lasted >2 mo and required both CD4+ and CD8+ T cells. Mature tumor capturing DCs stimulated the differentiation of P1A tumor antigen-specific, CD8+ T cells and uniquely transferred tumor resistance to naive mice. Therefore, the access of dying tumor cells to DCs that are maturing to activated NKT cells efficiently induces long-lived adaptive resistance.

scholarly journals Cancer Immunotherapy: Priming the Host Immune Response with Live Attenuated Salmonella enterica

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Marco Antonio Hernández-Luna ◽  
Rosendo Luria-Pérez
Keyword(s):  
Immune Response ◽  
Cancer Immunotherapy ◽  
Salmonella Enterica ◽  
Tumor Tissue ◽  
Tumor Antigens ◽  
Tumor Regression ◽  
Promising Alternative ◽  
Induce Tumor Regression ◽  
Potential Use

In recent years, cancer immunotherapy has undergone great advances because of our understanding of the immune response and the mechanisms through which tumor cells evade it. A century after the first immunotherapy attempt based on bacterial products described by William Coley, the use of live attenuated bacterial vectors has become a promising alternative in the fight against cancer. This review describes the role of live attenuated Salmonella enterica as an oncolytic and immunotherapeutic agent, due to its high affinity for tumor tissue and its ability to activate innate and adaptive antitumor immune response. Furthermore, its potential use as delivery system of tumor antigens and immunomodulatory molecules that induce tumor regression is also reviewed.

scholarly journals Tumor Antigen Cross-Presentation and the Dendritic Cell: Where it All Begins?

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Alison M. McDonnell ◽  
Bruce W. S. Robinson ◽  
Andrew J. Currie
Keyword(s):  
T Lymphocyte ◽  
Cd8 T Cells ◽  
Tumor Antigen ◽  
Antitumor Immunity ◽  
Tumor Antigens ◽  
Cytotoxic T Lymphocyte ◽  
Cross Presentation ◽  
Tumor Bearing ◽  
Antigen Presenting

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that are critical for the generation of effective cytotoxic T lymphocyte (CTL) responses; however, their function and phenotype are often defective or altered in tumor-bearing hosts, which may limit their capacity to mount an effective tumor-specific CTL response. In particular, the manner in which exogenous tumor antigens are acquired, processed, and cross-presented to CD8 T cells by DCs in tumor-bearing hosts is not well understood, but may have a profound effect on antitumor immunity. In this paper, we have examined the role of DCs in the cross-presentation of tumor antigen in terms of their subset, function, migration, and location with the intention of examining the early processes that contribute to the development of an ineffective anti-tumor immune response.

scholarly journals Sensitive identification of neoantigens and cognate TCRs in human solid tumors

2021 ◽  
Author(s):  
Marion Arnaud ◽  
Johanna Chiffelle ◽  
Raphael Genolet ◽  
Blanca Navarro Rodrigo ◽  
Marta A. S. Perez ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Antigen ◽  
Tumor Antigens ◽  
Low Frequency ◽  
Tumor Infiltrating Lymphocytes ◽  
Patient Specific ◽  
Specific Tumor ◽  
Human Solid Tumors ◽  
Xenograft Mice ◽  
Infiltrating Lymphocytes

AbstractThe identification of patient-specific tumor antigens is complicated by the low frequency of T cells specific for each tumor antigen. Here we describe NeoScreen, a method that enables the sensitive identification of rare tumor (neo)antigens and of cognate T cell receptors (TCRs) expressed by tumor-infiltrating lymphocytes. T cells transduced with tumor antigen-specific TCRs identified by NeoScreen mediate regression of established tumors in patient-derived xenograft mice.

scholarly journals Critical Role of Dendritic Cell–Derived IL-27 in Antitumor Immunity through Regulating the Recruitment and Activation of NK and NKT Cells

2013 ◽  
Vol 191 (1) ◽  
pp. 500-508 ◽  
Author(s):  
Jun Wei ◽  
Siyuan Xia ◽  
Huayan Sun ◽  
Song Zhang ◽  
Jingya Wang ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Antitumor Immunity ◽  
Critical Role ◽  
Nkt Cells

scholarly journals Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francesca Mancini ◽  
Gianmarco Gasperini ◽  
Omar Rossi ◽  
Maria Grazia Aruta ◽  
Maria Michelina Raso ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Critical Role ◽  
Shigella Sonnei ◽  
Added Value ◽  
Protein Antigens ◽  
Outer Membranes ◽  
O Antigen ◽  
Membrane Antigens ◽  
Specific Igg

AbstractGMMA are exosomes released from engineered Gram-negative bacteria resembling the composition of outer membranes. We applied the GMMA technology for the development of an O-Antigen (OAg) based vaccine against Shigella sonnei, the most epidemiologically relevant cause of shigellosis. S. sonnei OAg has been identified as a key antigen for protective immunity, and GMMA are able to induce anti-OAg-specific IgG response in animal models and healthy adults. The contribution of protein-specific antibodies induced upon vaccination with GMMA has never been fully elucidated. Anti-protein antibodies are induced in mice upon immunization with either OAg-negative and OAg-positive GMMA. Here we demonstrated that OAg chains shield the bacteria from anti-protein antibody binding and therefore anti-OAg antibodies were the main drivers of bactericidal activity against OAg-positive bacteria. Interestingly, antibodies that are not targeting the OAg are functional against OAg-negative bacteria. The immunodominant protein antigens were identified by proteomic analysis. Our study confirms a critical role of the OAg on the immune response induced by S. sonnei GMMA. However, little is known about OAg length and density regulation during infection and, therefore, protein exposure. Hence, the presence of protein antigens on S. sonnei GMMA represents an added value for GMMA vaccines compared to other OAg-based formulations.

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