ReeVa-Private Driver for Delivery of Antigens to DCs

In order to overcome the problem of cancer, scientists have made unremitting explorations and efforts from various angles. Dendritic cells, as important antigen-presenting cells, have naturally become the focus of research, which thus involves the question of how to improve the efficiency of DCs to present antigens. Creative Biolabs leads a top research team and has been developing cancer vaccines for over a decade. We have established multiple advanced platforms to facilitate the development of cancer vaccines and therapies, and ReeVa is one of the most promising representatives.

Background

Cytotoxic lymphocytes (CTLs) are considered to be the most critical and important cells for killing tumors in many different developmental stages or groups of T cells with different functions. Their targeting and specificity to tumor cells allows these cells to trace tumor cells in the human body once they are activated by tumor antigen signals, and inject cytotoxins into them to kill them and continue to find the next target. Therefore, the initiation of this specific immune response, the production of CTL becomes the goal of treatment of tumors. Dendritic cells are the most powerful full-time antigen-presenting cells in the immune system and are the only antigen-presenting cells that activate resting T cells. The study found that the majority of patients with a large number of infiltrating DCs in the solid tumor had a good prognosis. When the DC function is defective, the tumor cells would escape from the monitoring of immune system and grow indefinitely. The mechanism of anti-tumor immunity of the body includes cellular and humoral immunity, in which cellular immunity is the main force, but only when antigen-presenting cells successfully capture, process, and present tumor antigens, can initiate specific immune responses and establish effective anti-tumor immune response.

Brief schematic of CTL activation and killing of tumor cells. – Creative Biolabs

Fig.1 Brief schematic of CTL activation and killing of tumor cells.

ReeVa-Private Driver for Delivery of Antigens to DCs

As mentioned above, DCs play an important intermediate role in anti-tumor immune responses. Initiating CD8 T cell responses requires them to interact with antigen-presenting DCs via the MHC I pathway. Most of the current vaccines cross-present proteins through the MHC class II pathway, antigen presentation by MHC I pathway requires antigen expression in antigen-presenting cells, which is also thought to strongly induce CD8+ T cell responses. Therefore, efficient activation of DCs to further activate CTL cells and kill tumor cells has become a promising tumor treatment strategy. Based on this principle, we developed the re-engineered virus carrying tumor antigen platform (ReeVa platform). The platform reengineers the lentivirus to carry the whole, specific or neo-epitopes genetic information of the tumor antigen and selectively delivers the information to the DCs. The engineered, integration-deficient, non-replicating lentiviral vector contains envelope glycoprotein obtained from Sindbis virus and is capable of selectively targeting CD209 (DC-SIGN) on the surface of human immature DCs via this glycoprotein. Our re-engineered ReeVa vector specifically interacts with DCs after entering the body of cancer patient and delivers the information of the carried tumor antigen to the DCs in the form of RNA. DCs that have received tumor antigen RNA express it into protein, process it and present it to CD8 T cells, causing activation and division of CD8 T, producing a large number of CTLs to kill tumor cells that bear specific tumor antigens. Preclinical studies in animal models have shown that vaccines based on the ReeVa platform can effectively target DCs in mice, induce potent, multifunctional, long-lasting CD8+ T cell responses, and in tumor challenge experiments in different tumor models, they can also provide short-term or long-term immunity.

ReeVa Platform – Creative Biolabs

Features of ReeVa Platform

  • Specificity to DCs
  • Ability to induce maximum CTL response
  • Capable of carrying a variety of tumor antigens as well as immunostimulatory molecules
  • No pre-existing immunity to ReeVa vector
  • No risk of integration of ReeVa vector into the human genome
  • Flexibility and expandability

In order to develop effective cancer vaccines and therapies, scientists have explored and worked on different aspects. Improving the antigen-presenting ability of DCs and activating specific CTLs is one of the most promising options. Creative Biolabs, which has more than a decade of vaccine research history, has also invested a lot of energy in the prevention and treatment of cancer, and has achieved a series of gratifying fruits, and established a number of comprehensive platforms to help more cancer vaccine researchers accelerate their research process.


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