As HIV-specific cytotoxic T cells play a key role during acute and chronic HIV-1 infection in humans, the ability of potential anti-HIV vaccines to elicit strong, broad T cell responses is likely to be crucial. The HIV-1 Gag antigen is widely considered a relevant antigen for the development of an anti-HIV vaccine since it is one of the most conserved viral proteins and is also known to induce T cell responses. In the majority of studies reporting Gag-specific cellular immune responses induced by Gag-based vaccines, only a small number of Gag T cell epitopes were tested in preclinical mouse models, thus giving an incomplete picture of the numerous possible cellular immune responses against this antigen. As is, this partial knowledge of epitope-specific T cell responses directed to Gag will unavoidably result in a limited preclinical evaluation of Gag-based vaccines.

Results:

In this study we identified new Gag CD8+ T cell epitopes in BALB/c mice vaccinated with the HIV-1 Gag antigen alone or in combination with the HIV-1 Tat protein, which was recently shown to broaden T cell responses directed to Gag. Specifically, we found that CTL responses to Gag may be directed to nine different CTL epitopes, and four of these were mapped as minimal CTL epitopes.

Conclusion:

These newly identified CTL epitopes should be considered in the preclinical evaluation of T cell responses induced by Gag-based vaccines in mice.

PloS one3区 · 综合性期刊

Regulation of Gag- and Env-Specific CD8+ T Cell Responses in ART-Naïve HIV-Infected Patients: Potential Implications for Individualized Immunotherapy

3区 · 综合性期刊

ArticleOA

作者: Dyrhol-Riise, Anne-Ma ; Kvale, Dag ; Prebensen, Christian ; Lind, Andreas

Strategies to develop a functional cure for HIV infection will likely require boosting of effector T cell responses to eliminate reactivated, latently infected cells. We have recently explored an assay for assessing antigen-specific regulation of T cell proliferation, which was related to clinical progression in untreated patients and to vaccine efficacy in two trials of therapeutic Gag-based vaccines. We here expand the same assay to further investigate regulation mediated by various inhibitory pathways. Peripheral blood mononuclear cells from 26 asymptomatic HIV-infected, antiretroviral therapy-naïve patients were stimulated with Gag and Env overlapping peptide panels for 5 days. Monoclonal antibodies (mAbs) blocking inhibitory mediators interleukin (IL) 10, transforming growth factor (TGF) β, programmed death ligand (PD-L) 1 and herpes virus entry mediator (HVEM) were added to parallel cultures. Functional T cell regulation (FTR) was defined as the difference in proliferation between stimulated cultures with and without blocking mAbs. FTR was detected in 54% of patients. Blockade of IL-10/PD-L1 and IL10/TGF-β detected all cases with Gag- and Env-associated FTR, respectively. In accordance with previous findings, isolated Env FTR was associated with higher plasma HIV RNA and lower CD4 counts, while patients with both Gag and Env FTR also had higher Gag- and Env-specific proliferative CD8+ T cell responses. There was no association between FTR and frequencies of activated regulatory T cells. In conclusion, we observed substantial heterogeneity in FTR between patients, inhibitory pathways and HIV antigens. FTR may help to individualize immunomodulation and warrants further assessment in clinical immunotherapy trials.

项与 Therapore-based vaccines(AVANT Immunotherapeutics) 相关的新闻（医药）

2022-11-09

·BioSpace

IO Biotech Announces an Invited Oral Presentation and Two Poster Presentations with New Preclinical Data for Additional Pipeline Candidates at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting

- Preclinical data showing the rationale for two new pipeline candidates targeting the immunosuppressive effects of Arginase-1 (ARG1) and Transforming Growth Factor Beta 1 (TGFb1) were presented in two posters NEW YORK, Nov. 09, 2022 (GLOBE NEWSWIRE) -- IO Biotech (Nasdaq: IOBT), IO Biotech, a clinical-stage biopharmaceutical company developing novel, immune-modulating anti-cancer therapies based on its proprietary T-win® technology, today announced details of the invited oral presentation and two poster presentations at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting. Information for the invited oral presentation: Title: Utilizing Tumor Microenvironment Antigens for Immune Modulatory Vaccines Session: Concurrent Session 119 – Vaccines: In Situ Agents and Novel Systemic Approaches Presenter: Mads Hald Andersen, Ph.D. – Professor and Director of Center for Cancer Immune Therapy at Herlev University Hospital, IO Biotech Founder and Scientific Advisor Date: Thursday, November 10, 2022 Location and time: TBD – 6:25 p.m. EST “We are pleased that Dr. Andersen has been invited to SITC to give an overview of our Phase 1/2 MM1636 study at SITC and are very encouraged that the long-term follow up data confirm the earlier results reported from this study in front-line PD-1 naïve metastatic melanoma patients,” said Mai-Britt Zocca, Ph.D., President and Chief Executive Officer of IO Biotech. “We are also thrilled to share, for the first time, preclinical data from the next two candidates in our pipeline that target ARG1 and TGFβ1, immunosuppressive antigens found in the tumor microenvironment (TME).” Dr. Zocca continued, “Based on the promising clinical results of our lead asset, IO102-103, which dually targets and disrupts immunosuppressive antigens indoleamine 2,3-dioxygenase (IDO) and anti-programmed death ligand 1 (PD-L1), we believe that targeting suppressive antigens can not only better allow T-cells to directly attack tumor cells, but also modulate the TME as an immunotherapeutic approach. We see the potential of these two new candidates to build on the strength of our T-win® platform and a path forward for Investigational New Drug filings. We look forward to providing additional updates on both our Phase 3 trial with IO102-103 in combination with pembrolizumab for metastatic melanoma and our Phase 2 basket trial in solid tumors in the coming weeks and months.” Highlights from the two preclinical poster presentations include: Title: Modulating the TME by targeting TGFb1 with vaccine-induced immune responses Abstract Number: 1182 Presenter: Brian Weinert, Ph.D., Principal Scientist IO Biotech Date: Friday, November 11, 2022 Location and time: Poster Hall C Poster Hall Hours: 9 a.m.– 8:30 p.m. EST Transforming Growth Factor Beta 1 (TGFb1) is a major immune suppressive element in the tumor microenvironment (TME) of most solid tumors. It is implicated in antagonizing the efficacy of various immune oncology therapies. Developing selective and efficacious modulators of the pathway is an ongoing challenge in the field. IO Biotech has deployed its unique approach to modulate TGFb1 activity in the TME, and the poster details the identification and characterization of highly selective TGFb1 peptide vaccines. These peptides were shown to induce potent and selective immune responses (versus TGFb2 and TGFb3). Murine TGFb1 peptide vaccines were also identified and characterized, and functional activity was preliminarily demonstrated in a relevant murine tumor mouse model (MC38). Translational work detailing content and identity of cells expressing TGFb1 and other immune suppressive antigens in the TME provided the biological rationale to target TGFb1 via a vaccine approach individually and in combination with other TME targets. These preclinical data support further development of a TGFβ1 vaccine as a TME targeted approach for the treatment of a wide range of cancers. Title: An Arginase-1 peptide-based vaccine is an exciting approach to modulate the TME and drive efficacy in preclinical tumor models Abstract Number: 1440 Presenter: Marion Chapellier, Ph.D., Senior Scientist IO Biotech Date: Friday, November 11, 2022 Location and time: Poster Hall C Poster Hall Hours: 9 a.m.– 8:30 p.m. EST Arginase-1 (ARG1) regulates immune escape of tumor cells through various mechanisms in the tumor microenvironment (TME). It is being targeted experimentally in the clinic, but selective and efficacious inhibitors of ARG1 remain elusive. IO Biotech has shown that vaccination against TME targets is an exciting new therapeutic approach and has previously identified and characterized selective ARG1 peptide vaccines. The poster highlights translational data to guide clinical development of the vaccine in the relevant cancer indications and provides a biological rationale to combine an ARG1 vaccine with other TME vaccines (IDO1/PD-L1). In addition, in vivo data demonstrated functional efficacy of the murine ARG1 vaccine in two ARG1 expressing mouse cancer models in combination with other TME vaccines. These preclinical data support further development of an ARG1 vaccine as a TME vaccine targeted approach in combination with an IDO/PD-L1 vaccine for the treatment of a wide range of solid cancers and we anticipate an IND filing for IO112 (ARG1 vaccine) in 2023. About SITC Established in 1984, the Society for Immunotherapy of Cancer (SITC) is a nonprofit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC is comprised of influential basic and translational scientists, practitioners, health care professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC aims to one day make the word “cure” a reality for cancer patients everywhere. Learn more about SITC at sitcancer.org About IO Biotech IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulating cancer therapies based on its T-win® technology platform. The T-win® platform is a novel approach to cancer immunotherapy designed to activate naturally occurring T cells to target immunosuppressive mechanisms. IO Biotech is advancing in clinical studies its lead immuno-oncology candidate, IO102-IO103, targeting IDO and PD-L1, and through preclinical development its other pipeline candidates. IO Biotech is headquartered in Copenhagen, Denmark, with its United States headquarters in New York, New York. For further information, please visit . Forward-Looking Statement This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including regarding future clinical trials and results, are based on IO Biotech’s current assumptions and expectations of future events and trends, which affect or may affect its business, strategy, operations or financial performance, and actual results and other events may differ materially from those expressed or implied in such statements due to numerous risks and uncertainties. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Because forward-looking statements are inherently subject to risks and uncertainties, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements speak only as of the date hereof and should not be unduly relied upon. Except to the extent required by law, IO Biotech undertakes no obligation to update these statements, whether as a result of any new information, future developments or otherwise. Company Contact: Amy Sullivan Chief Financial Officer IO Biotech, Inc. asu@iobiotech.com Investor Contact: Corey Davis, Ph.D. LifeSci Advisors 212-915-2577 cdavis@lifesciadvisors.com Media Contact: Raena Mina, Ph.D. LifeSci Communications 646-606-1438 rmina@lifescicomms.com

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