Both DNA Cancer Vaccines Studied Were Derived from Immunomic’s UNITE™ Platform
Phase 1 Study of MCPyV-LT Vaccine in Merkel Cell Carcinoma to Begin in Q2
ROCKVILLE, Md.–(BUSINESS WIRE)–#AACR22–Immunomic Therapeutics, Inc., (“ITI”), a privately-held clinical-stage biotechnology company pioneering the study of LAMP-mediated nucleic acid-based immunotherapy, announced today that the data from two posters are being presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 held in New Orleans, Louisiana, from April 8-13. These posters to be presented at the AACR Meeting focus on the investigational nucleic acid platform, UNITE™ (UNiversal Intracellular Targeted Expression) for two vaccines, ITI-3000 for Merkel cell carcinoma (targeting the large T antigen of the Merkel cell polyomavirus) and Her2/Neu-LAMP DNA vaccine, both of which fuse a tumor associated antigen with lysosomal associated membrane protein 1 (LAMP-1). This proprietary lysosomal targeting technology results in enhanced antigen presentation and a balanced T cell response.
The posters are accessible on the “Posters” section of Immunomic Therapeutics’ website at: https://www.immunomix.com/media/posters/.
Highlights from the presentations are as follows:
Poster Number: 10
Title: “LAMP1 targeting of the large T antigen of Merkel cell polyomavirus elicits potent CD4+ T cell responses, tumor inhibition, and provides rationale for first-in-human trial”
Authors: Claire Buchta Rosean, PhD1; David M. Koelle, MD2; Paul Nghiem, MD, PhD3, Mohan Karkada, PhD1, Teri Heiland, PhD1
1Immunomic Therapeutics Inc., Rockville, MD, USA 2Department of Medicine/Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA 3Department of Medicine, Department of Dermatology, University of Washington, Seattle, WA, USA
- This presentation reports results of pre-clinical mouse studies of a cancer vaccine that promotes potent, antigen-specific CD4 T cell responses to MCPγV-LT. The majority of Merkel cell carcinomas (MCC), a rare and highly aggressive type of neuroendocrine skin cancer, are associated with Merkel cell polyomavirus (MCPyV) infection. MCPyV integrates into the host genome, resulting in expression of a truncated form of the viral large T antigen (LT) in infected cells, and makes LT an attractive target for therapeutic cancer vaccines.
- To activate antigen-specific CD4 T cells in vivo, the investigators utilized the nucleic acid vaccine platform, UNITE (UNiversal Intracellular Targeted Expression), which fuses a tumor-associated antigen with lysosomal-associated membrane protein 1 (LAMP1). LTS220A, encoding a mutated form of MCPγV-LT that diminishes its pro-oncogenic properties, was introduced into the UNITE platform. Mice were vaccinated with 40µg of ITI-3000 or control vector via intradermal injection and electroporation. A B16F10 melanoma line stably transduced to express LTS220A (B16-LT) was injected subcutaneously in the right flank.
- Vaccination with LTS220A-UNITE (ITI-3000) induced antigen-specific CD4 Th1 cells that was associated with delayed tumor growth and enhanced survival in treated mice in both the prophylactic and therapeutic settings. This effect was dependent on the CD4 T cells ability to produce IFNγ (interferon gamma), suggesting the potential mechanism of action of ITI-3000. In addition, ITI-3000 induced changes in the tumor microenvironment, including increased numbers of CD4 and CD8 T cells, reduced frequency of myeloid cells, and enhanced pro-inflammatory cytokine production.
Poster Number: 3
Title: “Harnessing soluble CD40L to enhance anti-tumor efficacy of Her2-LAMP DNA vaccine using UNITE platform”
Authors: Wei Shen1, Renhuan Xu2, Yun-Ting Kao1, Mohan Karkada1, and Teri Heiland1
1Immunomic Therapeutics, 15010 Broschart Road, Rockville, MD 20850 2ARV-Tech, Rockville, MD 20852
- This presentation reports results of preclinical mouse studies on a HER2/Neu-LAMP DNA vaccine that included a bicistronic DNA construct in which both the tumor antigen (HER2) fused with LAMP-1 (lysosomal- associated membrane protein 1) and sCD40L were expressed separately. CD40 ligand (CD40L; CD154) is a transmembrane protein expressed on the surface of activated T cells, particularly on CD4 T cells, which stimulates CD40-dependent activation of antigen-presenting cells (APCs), resulting in enhancement of T cell and antibody responses.
- To elicit cellular and humoral responses, the investigators employed the proprietary UNITE (UNiversal Intracellular Targeted Expression)-VAX platform, which utilizes a plasmid DNA expressing TAAs and LAMP to deliver TAAs to the MHC II compartment, thus potentially enhancing both antibody generation and CD4+ T cell response. Mice were immunized intradermally with 20µg of control vector, HER2-LAMP, or bicistronic-HER2-LAMP-sCD40L.
- Vaccination with HER2-LAMP-sCD40L was associated with the detection of soluble forms of CD40L in the supernatant of HER2-LAMP-sCD40L transfected 293T cells: this soluble CD40L may function to enhance vaccine immunogenicity. The HER2-LAMP-sCD40L DNA vaccine elicited a robust HER2- specific cellular and humoral response; of note, CD4 T cells were elevated as compared with CD8 T cells, suggesting that sCD40L preferentially acts on CD4 T cells in vivo. The HER2-LAMP-sCD40L DNA vaccine exhibited significant antitumor effect in a murine breast tumor model.
“Based on these preclinical findings, we are planning a first-in-human Phase 1 open-label study to evaluate the safety, tolerability, and immunogenicity of ITI-3000 in Merkel cell carcinoma patients,” stated Dr. William Hearl, Chief Executive Officer of Immunomic Therapeutics. “This study will be our second clinical study utilizing our proprietary nucleic acid vaccine platform UNITE and underscores the potential for our platform to design and introduce novel cancer vaccines for hard-to-treat cancers.”
“We are highly encouraged by the data from the preclinical development for Her2-LAMP-sCD40L vaccine,” stated Teri Heiland, PhD, Chief Scientific Officer of Immunomic Therapeutics. “The prolonged survival noted in the murine model suggests that this novel bicistronic vaccine may be an effective strategy to promote anti-tumor efficacy in vivo for multiple HER2-expressing cancer types.”
About UNITE™
ITI’s investigational UNITE™ platform, UNiversal Intracellular Targeted Expression, leverages the ability to engineer chimeric proteins, directing antigen presenting cells to present antigens to the immune system through a targeted pathway and driving a robust immune response. UNITE vaccines are distinct in that they combine two components: nucleic acid constructs that encode a specific antigen and an endogenous Lysosomal Associated Membrane Protein (LAMP-1) sequence. The UNITE platform harnesses LAMP-1 as a means of presenting the vaccine target to the immune system, resulting in antibody production, inflammatory cytokine release, and establishing critical immunological memory, something that other vaccine approaches commonly lack. This approach could put UNITE technology at the crossroads of immunotherapies in multiple indications, including cancer, human allergy, animal health, and infectious disease. Preclinical data is currently being developed to explore whether LAMP-1 nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and used to create immune responses in tumor types that otherwise do not provoke an immune response.
About Immunomic Therapeutics, Inc.
Immunomic Therapeutics, Inc. (ITI) is a privately held, clinical stage biotechnology company pioneering the development of vaccines through its proprietary technology platform, UNiversal Intracellular Targeted Expression (UNITE™), which is designed to utilize the body’s natural biochemistry to develop vaccines that generate broad immune responses. UNITE has a robust history of applications in various therapeutic areas, including infectious diseases, oncology, allergy, and autoimmune diseases. ITI is primarily focused on applying the UNITE platform to oncology, where it could potentially have broad applications, including antigen-derived antibodies as biologics. The Company has built a pipeline leveraging UNITE with programs in oncology, animal health, infectious disease, and allergy. ITI maintains its headquarters in Rockville, Maryland. For more information, please visit www.immunomix.com.
Contacts
Company:
Melissa Kemp
mkemp@immunomix.com
301-968-3501
ITI Media:
Melody Carey
mcarey@rxir.com
917-322-2571