LAMP-Vax™, A NEW APPROACH TO DNA VACCINES THAT ACHIEVES AN ENHANCED IMMUNE RESPONSE
Lysosomal Associated Membrane Protein (LAMP) is a glycoprotein found on 80% of the surface area of the lysosomal membrane. LAMP-vax™ DNA vaccines utilize the natural biochemistry of LAMP to intersect with the process that Antigen Presenting Cells, APCs use to internalize, digest, and present exogenously derived antigens to the immune system as part of the lysosomal/MHC-II complex. The result is enhanced antigen presentation and a greatly enhanced immune system response to a vaccine.
Upon immunization with a LAMP-vax™ DNA vaccine, APCs take up the DNA and produce the encoded protein sequence inside the cell as part of a fusion protein with LAMP.
In this way, LAMP-DNA vaccines activate APCs to the immunized antigen(s) through the CD4+ helper T-cell pathway. LAMP-DNA immunization contrasts with the immune response to conventional DNA vaccines, which are processed and primarily presented through MHC-I and elicit a cytotoxic T response. LAMP-vax™ DNA plasmids show no decrease in CD8+ cytotoxic T-cell response yet also feature a CD4+ response. This initiates a more complete immune response including antibody production, cytokine release and critical immunological memory.
Conclusion: LAMP-vax vaccines active the entire immune system.
COMPETITIVE ADVANTAGES OF LAMP TECHNOLOGY
MHC-II Targeting Strategy Necessary
MHC-II antigen presentation is key to improving DNA vaccines and increasing the likelihood of clinical success. The addition of LAMP Technology to DNA vaccine design is necessary to avoid the limited immune response that occurs when antigen is processed in somatic cells and presented through the generic MHC-I pathway. By accessing the MHC-II antigen presentation pathway, LAMP-vax vaccines induce high titers of protective or therapeutic antibodies and cell-mediated immunity.
For Lysosomal Targeting, a Stabilization Domain is Required
The luminal domain of LAMP stabilizes the antigenic-fusion protein and the glycosylated domain protects the antigenic sequence from premature proteolysis, while permitting proteolysis in mature lysosomes. Including the LAMP luminal domain in a LAMP-antigen vaccine enhances protein expression, antigen accumulation in MHC-II containing lysosomes, and the breadth and scope of immune response.
Proven Safety in the Clinic
The LAMP-vax platform has been clinically tested, which has shown that LAMP-vax is safe and well tolerated in diverse populations of patients, including allergic subjects and cancer patients. High risk AML subjects were given the cancer vaccine, GRNVAC1, in a Phase II study sponsored by the Geron Corporation. The clinical experience of these patients demonstrates that the LAMP formulation is safe and well tolerated, with some patients receiving up to 30 injections of therapy. An earlier Phase I study of GRNVAC1 in prostate cancer patients also revealed a strong interferon-gamma response and a boostable memory capability. Further, it is recent in-house development of JRC-LAMP-Vax in a Phase IA & IB study showed safety and immunogenicity in the way of skin test conversions in allergic patients.
LAMP-vax vaccines have been developed that immunize against multiple antigens simultaneously. For allergy indications, this allows the commercial development of vaccine candidates that simultaneously address multiple allergens. Likewise, for the cancer market, this has strong advantages over other approaches that only deliver one antigen or antigenic epitope at a time.
Plug & Play Vaccine Design for Rapid Product Line Development
LAMP-vax vaccines utilize a standardized plasmid backbone that includes the appropriate LAMP elements. The target antigen is inserted into this plasmid easily at a multi-cloning site and then validated for proper expression characteristics. This process takes only 30 days in design and development and 30 days for validation of the construct. Thus, any given target can be developed into a working vaccine candidate (or component of a multi-vector formulation) within a business quarter and with limited expense. This versatility enables ITI to quickly expand both its product line and that of its partner companies.
ADDITIONAL KEY FEATURES OF DNA VACCINES THAT LAMP INCORPORATES
Improved plasmid design
Next generation DNA vaccines are using improved origins, promoters, encoding multiple proteins in one plasmid, including polyadenylation signal. Immunomic Therapeutics’ LAMP Vax is on the cutting edge of improved plasmid design, incorporating Nature’s high-yield, antibiotic free, efficient immunization vector with ITI’s proprietary LAMP sequence which facilities MHC-II targeting. Further, LAMP-based plasmids utilize the Nature’s HyperGRO process, a proprietary fermentation/manufacturing process which produces higher yields of DNA, enabling better scale-up manufacturing and lower cost vaccines.
Improved design to enhance immunogenicity
Codon optimization, removal of untranslated regions, inclusion of CPG motifs. These are just some design features of today’s DNA vaccines. ITI incorporates some of these new features into LAMP-Vax but beyond this, our in-house molecular biology team are experts in optimizing the design of our DNA vaccines through additional methods.
Various delivery systems Various approaches to delivery of DNA vaccines have arisen over the past several years.
These include direct injection, liposomes, particle mediated (e.g., gold coated particles), and electroporation. Our first-class R&D team continues to advance LAMP in collaboration with cutting-edge delivery technologies to make sure we are delivering the most properly designed vaccines to the right immune cell populations in the body. Currently, we are collaborating with Bioject Technologies, Inc., whose pain-free intradermal delivery system shows great promise with LAMP-Vax.
Immunomic Therapeutics, Inc.
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