Definition of Key Variables for the Induction of Optimal NY-ESO-1–Specific T Cells in HLA Transgene Mice

Johannsen, Alexandre; Genolet, Raphaël; Legler, Daniel F.; Luther, Sanjiv A.; Luescher, Immanuel F.

doi:10.4049/jimmunol.1001397

Cited by 9 publications

(6 citation statements)

References 50 publications

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“…The therapeutic efficacy was associated with a Th1/Tc1 cytokine profile consisting of increased IFN-γ, TNF-α, and IL-2 cytokine production and a concomitant decrease in Th2 cytokines such as IL-4, IL-5, and IL-13. We also observed a significant increase in CCL3 (MIP-1α) and CCL4 (MIP-1β) chemokine expression, 19 which have been shown to enhance CD8 + T cell differentiation and dendritic cell function 32-35 . Additional studies are underway to elucidate the mechanisms by which CCL3 and/or CCL4 affect CD8 + T cell expansion and effector function following combination immunotherapy.…”

mentioning

confidence: 63%

Combinatorial immunotherapeutic approaches to restore the function of anergic tumor-reactive cytotoxic CD8⁺ T cells

Redmond

Linch

2016

Human Vaccines & Immunotherapeutics

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Numerous preclinical studies have demonstrated that combination immunotherapy can significantly reduce tumor growth and improve overall survival as compared to monotherapy. Furthermore, dual CTLA-4/PD-1 checkpoint blockade recently received FDA-approval for patients with metastatic melanoma, becoming the first combination immunotherapy to garner this designation in a rapidly evolving field. Despite this progress, the majority of patients do not respond to treatment, underscoring the critical need for more effective therapies. We have been investigating the mechanisms by which combination immunotherapy with an OX40 agonist plus CTLA-4 checkpoint blockade augments effector T cell responses to elicit anti-tumor immunity. Surprisingly, this approach failed to eradicate well-established tumors, in part due to the induction of anergy in cytotoxic CD8+ T cells. Further work revealed that anergic CD8+ T cells could be rescued by combining a dendritic cell-targeted vaccine with combination immunotherapy. Taken together, these data suggest that novel combinatorial immunotherapeutic strategies incorporating a vaccination strategy may be needed to generate effective anti-tumor responses in the majority of patients with metastatic disease.

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mentioning

confidence: 63%

Combinatorial immunotherapeutic approaches to restore the function of anergic tumor-reactive cytotoxic CD8⁺ T cells

Redmond

Linch

2016

Human Vaccines & Immunotherapeutics

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“…Johannsen and colleagues revealed that the T-helper (T H )1-associated cytokines IFN-g and IL-2 played key roles in CTL priming by upregulating the chemokine receptor on naive CD8 þ T cells (36). IFN-g induces T H 0 cells to differentiate toward T H l cells, promoting the T H l cell response and thus regulating the balance of T H l/T H 2 (37).…”

Section: Discussionmentioning

confidence: 99%

Multiple Antigenic Peptides Based on H-2Kb–Restricted CTL Epitopes from Murine Heparanase Induce a Potent Antitumor Immune ResponseIn Vivo

Tang

Wang

Guo

et al. 2012

Molecular Cancer Therapeutics

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Accumulating research suggests that heparanase may be a universal tumor-associated antigen (TAA). Several heparanase T-cell epitopes from humans and mice have already been identified. However, because of low immunogenicity, polypeptide vaccines usually have difficulty inducing effective antitumor immune responses in vivo. In this study, to increase the immunogenicity of polypeptide vaccines, we designed and synthesized two four-branch multiple antigenic peptides (MAP) on the basis of mouse heparanase (mHpa) Tcell epitopes (mHpa398 and mHpa519). The dendritic cells (DC) from mice bone marrow loaded with above MAP vaccines from heparanase were used to evaluate immune response against various tumor cell lines, compared with immune response to their corresponding linear peptides, ex vivo and in vivo. We further assessed IFN-g release both in CD4 þ T-cell-depleted and nondepleted mice. The results showed that effectors generated from DCs, loaded with MAP-vaccinated mice splenocytes, induced a stronger immune response against target cells expressing both heparanase and H-2K b than did effectors generated from mice vaccinated with their corresponding linear peptides. Heparanase-specific CD8 þ T-cell responses induced by MAP and linear peptide vaccination required synergy of CD4 þ T cells. In addition, heparanse-derived MAP vaccines significantly inhibited the growth of B16 murine melanoma in C57BL/6 mice, while also increasing the survival rate of tumor-bearing mice. Our data suggest that MAP vaccines based on T-cell epitopes from heparanase are efficient immunogens for tumor immunotherapy.

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“…Different homologous and heterologous prime-boost vaccine strategies are currently being tested in the effort to develop effective vaccine responses against AIDS, as well as other infectious diseases and cancer and hold significant promise [117][118][119][120][121][122]. A sequential vaccination with DNA prime and recombinant viral vectors encoding multiple HIV genes boost has proven effective in eliciting robust CD8 + T cell responses in multiple animal models [38] as well as humans [121,123].…”

Section: Generation Of Functional Active Hiv-1-specific Immune Responmentioning

confidence: 99%

Simultaneous Approach Using Systemic, Mucosal and Transcutaneous Routes of Immunization For Development of Protective HIV-1 Vaccines

Im¹,

Jd²

2011

CMC

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Mucosal tissues are major sites of HIV entry and initial infection. Induction of a local mucosal cytotoxic T lymphocyte response is considered an important goal in developing an effective HIV vaccine. In addition, activation and recruitment of memory CD4(+) and CD8(+) T cells in systemic lymphoid circulation to mucosal effector sites might provide the firewall needed to prevent virus spread. Therefore a vaccine that generates CD4(+) and CD8(+) responses in both mucosal and systemic tissues might be required for protection against HIV. However, optimal routes and number of vaccinations required for the generation of long lasting CD4(+) and CD8(+) CTL effector and memory responses are not well understood especially for mucosal T cells. A number of studies looking at protective immune responses against diverse mucosal pathogens have shown that mucosal vaccination is necessary to induce a compartmentalized immune response including maximum levels of mucosal high-avidity CD8(+) CTL, antigen specific mucosal antibodies titers (especially sIgA), as well as induction of innate anti-viral factors in mucosa tissue. Immune responses are detectable at mucosal sites after systemic delivery of vaccine, and prime boost regimens can amplify the magnitude of immune responses in mucosal sites and in systemic lymphoid tissues. We believe that the most optimal mucosal and systemic HIV/SIV specific protective immune responses and innate factors might best be achieved by simultaneous mucosal and systemic prime and boost vaccinations. Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection.

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Definition of Key Variables for the Induction of Optimal NY-ESO-1–Specific T Cells in HLA Transgene Mice

Abstract: Material

Cited by 9 publications

References 50 publications

Combinatorial immunotherapeutic approaches to restore the function of anergic tumor-reactive cytotoxic CD8⁺ T cells

Combinatorial immunotherapeutic approaches to restore the function of anergic tumor-reactive cytotoxic CD8⁺ T cells

Multiple Antigenic Peptides Based on H-2Kb–Restricted CTL Epitopes from Murine Heparanase Induce a Potent Antitumor Immune ResponseIn Vivo

Simultaneous Approach Using Systemic, Mucosal and Transcutaneous Routes of Immunization For Development of Protective HIV-1 Vaccines

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Definition of Key Variables for the Induction of Optimal NY-ESO-1–Specific T Cells in HLA Transgene Mice

Abstract: Material

Cited by 9 publications

References 50 publications

Combinatorial immunotherapeutic approaches to restore the function of anergic tumor-reactive cytotoxic CD8+ T cells

Combinatorial immunotherapeutic approaches to restore the function of anergic tumor-reactive cytotoxic CD8+ T cells

Multiple Antigenic Peptides Based on H-2Kb–Restricted CTL Epitopes from Murine Heparanase Induce a Potent Antitumor Immune ResponseIn Vivo

Simultaneous Approach Using Systemic, Mucosal and Transcutaneous Routes of Immunization For Development of Protective HIV-1 Vaccines

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Combinatorial immunotherapeutic approaches to restore the function of anergic tumor-reactive cytotoxic CD8⁺ T cells

Combinatorial immunotherapeutic approaches to restore the function of anergic tumor-reactive cytotoxic CD8⁺ T cells