Immunotherapy is a novel mode of anti-cancer therapy, where the anti-cancer effect is mediated through patients own immune cells to fight cancer cells. It is a rapidly advancing field of translational science and it has been recognized as the ‘Top Breakthrough of the Year 2013’ by the journal “Science”. There are different modes of Immunotherapy to mediate the immune cells to kill the cancer cells and it could be either cell based or molecule based. Cell based immunotherapy utilizes activated immune cells including dendritic cells, natural killer cells, and T-cells for the killing of cancer cells.
DendroVac-CT is a novel, personalized, autologous dendritic cell based cellular immunotherapy for the treatment of cancers.
Dendritic cells are the most potent antigen presenting cells in human and animals. They play important role in recognizing the foreign antigens to fight and eliminate the invading microbes. They execute this function indirectly through the T cells by presenting the antigens to them and acquiring specificity to them through T cell receptor rearrangement. By this way, one dendritic cell can generate thousands of antigen specific T cells, which can kill millions of cancer cells. Dendritic cells can truly unleash the potential of T cells to kill the cancer cells. The Dendritic cells were first discovered in mice by Prof. Steinman in Rockefeller University in 1973 as a subset within macrophages. Later, the presence of dendritic cells in human and other animals was also discovered and this discovery was recognized with Nobel Prize in 2011. In the last four decades, the field of dendritic cell biology has expanded with large volume of scientific research and an US-FDA approved therapy for prostate cancer. Hundreds of clinical trials have been conducted on dendritic cell therapy for the treatment of cancer and several clinical trials are on-going. Dendritic cell therapy is a mode of cellular therapy using activated autologous dendritic cells to treat cancer. Monocyte-derived dendritic cells are the most common type of dendritic cells used for this purpose. In this process, the blood monocytes are isolated from the blood, differentiated into immature dendritic cells, activated using various activating factors in the presence or absence of tumor antigens. The activated dendritic cells has increased ability to interact with T cells, efficiently present antigen, profoundly activate, and promote their clonal expansion. Upon injection of these differentiated and activated dendritic cells back into the same patient, a potent T cell mediated immune response against the cancer cells in induced, which results in profound killing of cancer cells.
ImmunoVac-CT is a novel multiple cell immunotherapy platform for achieving most potent anti-cancer effect against solid tumors.
It has three different cellular component including activated NK cells, activated gamma delta T cells, and activated alpha beta T cells. Natural Killer (NK) cells were first described in 1975 as a distinct subset of lymphocytes, which are larger in size than T and B lymphocytes. NK cells are lymphocytes of the innate immune system. They are cytokine producing and have cytotoxic ability to kill tumor cells. Unlike T cells and B cells, NK cell recognition is not governed by high-resolution antigen specificity. Tumor cell recognition is mediated by the signals delivered through several activating and inhibitory receptors. The balance between activating and inhibitory signals decides the response of NK cells. Tumor cells downregulate their MHC-I molecules to escape from cytotoxic T cell mediated killing through adaptive immunity. When a NK cell confronts a tumor cell without expression of self-MHC class I molecules, the inhibitory signals are not active and the NK cell gets activated. They also showed profound tumor cell killing property without any need for prior immune sensitization of the host or antigen presentation. In humans, NK cells are characterized by expression of surface markers CD56 (NCAM-1) and CD16 (FcRIII). Functionally, NK cells are capable of killing as well as inducing tolerance depending on their activation state. In normal steady state, they express both activating and inhibitory receptors, where the resulting effect depends on the balance of engaged activating and inhibitory receptors. NK cells play a critical role in cellular host immunity against cancer, and the cancer cells also develop mechanisms to escape NK cell mediated immunity. Currently, the most common NK cell-based cancer immunotherapy approach is based on the adoptive transfer of expanded autologous NK cells. However, stable allogeneic NK cells, genetically modified NK cells, etc have also been used to a limited extent. Adoptively transferred ex vivo expanded activated autologous NK cells have been shown to improve clinical responses without any obvious adverse side effects in patients against different cancers including metastatic renal cell carcinoma (RCC), malignant glioma, and breast cancer. NK cells have the ability to recognize the cancer cells and kill them directly. They can also recognize antibody-coated target cells and trigger NK cell-mediated immune response resulting in rapid killing of cancer cells. Gamma delta T cells (γδ T cells) are a specialized small subset of CD3+ T cells having distinct γδ T-cell receptor (TCR) on their surface. They are different from the vast majority of other T cells which harbor αβ TCR. They also lack the CD4 or CD8 molecules on their surface. γδ T cells are a bridge between innate and adaptive responses due to their ability to rearrange T cell receptor (TCR) genes to produce functional diversity, maintain a memory phenotype, and their innate ability to use their TCR as a pattern recognition receptor to recognize the conserved antigens of pathogens and abnormal cells such as cancer cells. γδ T cells expressing Vγ9Vδ2 T cell receptor recognize the endogenous pool of isopentenyl pyrophosphate (IPP) that is overproduced in cancer cells as a result of dysregulated mevalonate pathway. The activated γδ T cells are very attractive for cell based cancer therapies due to their capacity to infiltrate tumors, exhibit MHC-unrestricted cytotoxicity for killing cancer cells, and their ability to secrete different cytokines. In general, the γδ T cell based cancer therapy relies upon either in vivo activation with phosphor-antigen and cytokines or on the adoptive transfer of ex vivo activated and expanded autologous γδ T cells. The γδ T cell based therapy has been tested in several clinical trials. αβ T cells are the most abundant conventional T cells present in the human peripheral blood. They work in a highly specific manner against the specific antigen presented by antigen presenting cells through MHC restriction. The harvested total population of αβ T cells would constitute certain number of T cells specific to the cancer antigen. Activating them and expanding them would be a great advantage to kill the cancer cells in a very specific manner. These cells have been tested and used in human clinical trials for more than three decades.
BioCAR is an engineered T cell therapy platform using chimeric antigen receptor (CAR) T cells. CAR-T cell therapy is the most promising therapy for treating certain types of Lymphoma and leukaemia.
It is major breakthrough in curing cancers and it is the first engineered living cell therapy recognized as drug. In CAR T-cell therapy, blood is taken from a patient and sent to a lab where the T cells are separated. These T cells are then modified to express a specific receptor that will allow the engineered T cell to find and kill the cancer cell. These engineered T cells are then multiplied in the lab and eventually given back to the patient through an intravenous infusion. Unlike T-cell receptor recognition of processed antigen presented by antigen presenting cells, the chimeric antigen receptor in CAR T cells can recognize the antigen present on the cancer cells directly without any need for antigen presenting cells. The engineered CAR on the T cells mediate targeted killing of cancer cells. Recently developed CAR T cells based therapeutic approach targeting malignant B-cells has been shown to be extremely potent to eliminate leukemic cells and bring complete cure in majority of the patients who had relapsed and recurrent disease. We have planned development of multiple product pipeline using this technology for treating different cancers.