Immunomic Therapeutics’ investigational LAMP-Vax platform is thought to work by encoding the Lysosomal Associated Membrane Protein, an endogenous protein in humans. In this way, Immunomic Therapeutics’ vaccines (DNA or RNA) have the potential to utilize the body’s natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach could put LAMP-Vax technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. LAMP is currently being employed in Phase II clinical trials as a cancer immunotherapy.
We are also collaborating with academic centers and biotechnology companies to study the use of LAMP in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. We believe that these early clinical studies may provide a proof of concept for LAMP-Vax therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.
Mode of Action
At the core of the work we do is LAMP-Vax, a chimeric, nucleic acid investigational vaccine that is believed to leverage a trafficking signal which guides the antigen to the lysosomes in antigen presenting cells. This proposed mechanism may play a part in an important aspect of immunology: the presentation of the antigen to T cells. In this case, because the antigen is fused to LAMP (Lysosomal Associated Membrane Protein), it is compelled to enter a pathway that results in the presentation of the antigen to CD4+ cells, often referred to as “helper T cells”. CD4+ T cells are involved in affecting many aspects of a complex immune response: cytokine release, immunological memory, antibody production, and support for other T cell types.
LAMP-Vax also appears to drive the orientation of the CD4+ T cell to a particular sub-type, the Th1 T cell. Th1 cells produce inflammatory and immunity inducing chemical messengers, cytokines, that can help stimulate the immune response. These factors are currently under intense focus in the cancer immunotherapy landscape. It is important to note that, while the mechanism of LAMP-Vax appears to focus on enhancing presentation of antigen to CD4+ T cells and producing a Th1 type CD4+ T cell response (an aspect missing in other platforms), LAMP-Vax is also believed to induce a broad immune response and thereby results in enhanced CD8+ T cell responses as well.
Reversing the “net allergic charge” and changing an IgE / Th2 allergic response into an IgG / Th1 response
Generating high affinity tumor antigen specific T cells supported by CD4 helper T-cells
Trafficking antigens into the MHC-II compartment for direct, antigen specific activation of CD4+ T cells
Our allergy assets remain an underpinning of Immunomic Therapeutics’ success, and have enabled our pivot to focus on oncology.
In addition to our canine atopic dermatitis vaccine concept, our vaccines using LAMP have already been tested in several clinical studies in both allergy and oncology.
In expanding the work being done that populates our pipeline, three distinct programs have been developed that focus on slightly different approaches in oncology. The antigens present in different types of cancer can be classified into the following classes: viral, neoantigens, and other cancer antigens. Viral antigens comprise targets that are either associated with or directly cause certain cancers. A class called neoantigens are those which are derived from gene mutations. Other cancer antigens can be further divided into various sub-types, but many of them are marked by incorrectly timed or inappropriately expressed levels of specific proteins. Our focus on these classes will accelerate into development as we move into 2018.
We know that there are multiple aspects that inform our platform's success. While research is the essential engine that drives our technology forward, our efforts in process development, manufacturing management, and regulatory affairs are critical factors that advance the Immunomic Therapeutics vision.
- We have significant capabilities in molecular biology, including nucleic acid vaccine design, immunology, and tumor mouse modeling. Since the Astellas deals, we have nearly doubled our research team to include deeper oncology expertise, including vaccinology, even neoantigen vaccine specialization. We now have a well-defined process to take things from ideation to in vivo animal proof of concept studies before handing them off to product development.
- Immunomic Therapeutics' continued investment in Process Development provides value in several ways. Internally, we are able to supply the R&D Team with LAMP-Vax products in a timely manner for their ongoing oncology studies. Additionally, our expanded capabilities allow us to work with our corporate partners to better understand and develop the manufacturing process and product testing assays.
- Our company has the capability to successfully plan, design and conduct clinical studies that enable us to establish POC in humans in a timely manner with the underlying capabilities to manufacture clinical trial supplies.
Over 100 studies have been published on LAMP, ranging from those focused on the fundamental biology of lysosomal associated membrane protein to the immunobiology of novel vaccine candidates. Of special note are the following publications:
To browse the literature, please see the curated list at PubMed.