Cancer Immunotherapy Rationale
There have been tremendous advances in approaches that harness the body’s own immune system to recognize and eliminate cancers. Currently approved approaches have focused on checkpoint inhibitors that interfere with the tumor’s ability to escape immune surveillance. Despite these advances, approved uses are limited to tumor types. Additionally, whether or not solid tumors respond is correlated with the presence of tumor infiltrating lymphocytes (TILs). In many tumors, TILs are either unable to infiltrate the tumor successfully or altogether absent. In these cases, complementary technologies are needed to overcome this barrier.
LAMP-Vax Cancer Vaccines
We believe that LAMP-based nucleic acid immunotherapies have the potential to broaden the current use of cancer immunotherapy by complementing approved and investigational approaches. Preclinical data suggest that LAMP-based nucleic acid immunotherapy has potential as a cancer immunotherapy in two general ways:
- Activation of the immune system against highly immunogenic tumor types, potentially amplifying the response seen with checkpoint inhibitors
- Creation of a new, robust immune response to tumor types that do not otherwise provoke an immune reaction, by reconfiguring a critical component of our immune system
LAMP containing constructs have the potential to reprogram the immune system in several specific ways:
- Create a polyfunctional immune response
- Activate the CD4+ T cell, a critical component of how the immune system fights cancer
- Induce antigen-specific Th1-biased TILs at the tumor site and activate CD8+ T cells
Our attention is focused on addressing the devastating disease, Glioblastoma Multiforme (GBM). With a median overall survival of about 16 months, there is a dire need to address this cancer. In addition to the clinical trials using LAMP-based technology, we now have an exclusive license with Annias Immunotherapeutics, a privately held Immuno-oncology company, for rights to intellectual property related to targeting antigens of cytomegalovirus (CMV) in cancer as well as methods of improving cancer vaccination. The detection of cytomegalovirus (CMV) antigens in malignant cells has suggested that treatment strategies based on immunological intervention, such as adoptive transfer of antiviral T cells or vaccination with viral epitopes, could be exploited as cancer therapy (Schuessler A, Walker DG and Khanna R (2014) Cytomegalovirus as a novel target for immunotherapy of glioblastoma multiforme. Front. Oncol. 4:275. doi: 10.3389/fonc.2014.00275).
For a deeper look at the clinical trials and studies related to our technology:
Vaccine Therapy for the Treatment of Newly Diagnosed Glioblastoma Multiforme (ATTAC-II)
Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (ATTAC)
Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination (Clinical Cancer Research)
Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients (Nature)
The Current Focus on the Role of CD4+ T Helper Cells in Cancer
To date, most in oncological settings have focused on the CD8+ killer T cell, for example, reprogramming them to kill tumor cells and showing at times dramatic effects in early clinical studies, especially in blood cancers like B-cell Lymphoma. These include approaches utilizing monoclonal antibodies and engineered autologous CD8+ T cells, such as CAR T and TCR transduced cells for adoptive cell therapy. These approaches show significant promise, but may not be the end-all be-all.
A new interest has emerged on the CD4+ helper T cell and its role in anti-tumor responses. This renewed focus on the importance of this cell population is in part due to advances in the fundamental understanding of immunology and its application in cancer, as well as the massive investment in translational clinical science brought about by industry focus on the PD-1/PD-L1 class of therapeutic antibodies.
We believe that the LAMP-Vax platform offers several differentiated advantages to other approaches. We feel that we may have one of the only ways of directly trafficking antigens into the MHC-II compartment for direct, antigen specific activation of CD4+ T cells.
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