Cancers belong to a group of diseases characterized by an uncontrolled growth of abnormal cells that can also have the ability to invade healthy tissues. Dependent on the cancer type, patients can be treated with a combination of surgery, radiotherapy, chemotherapy, targeted therapy and more recently immunotherapy.
Immunotherapies include all treatments where the immune system is modulated, such as passive immunotherapies, immuno-modulators, adoptive transfers and cancer vaccines. The latter must be differentiated into two distinct approaches: prophylactic and therapeutic cancer vaccines. Prophylactic cancer vaccines are administered to protect the healthy people against the development of a cancer. In contrast, therapeutic cancer vaccines are administered to cancer patients in order to strengthen the capability of their immune system to recognize and kill tumor cells.
Therapeutic Cancer Vaccines
The main goal of therapeutic cancer vaccines is to generate T cells able to specifically kill the tumor cells. To achieve a potent immune response, tumor antigens must be delivered to Antigen Presenting Cells, particularly dendritic cells (DCs), to allow cancer immunity to be initiated. The DCs process these antigens into small peptides (epitopes) that are presented on the cell surface either by MHC class I or MHC class II molecules allowing the activation of CD8+ cytotoxic T lymphocytes (CTLs) or CD4+ helper T (Th) cells, respectively. Based on current knowledge in immunology, induction of a tumor specific immune response requires three main steps:
- An antigen must be delivered to dendritic cells, which will process it into epitopes
- Dendritic cells should receive a suitable activation signal
- Activated tumor antigen-loaded dendritic cells must generate T-cell mediated immune responses in the lymphoid organs.
Induction of an immune response: dendritic cells process an antigen into peptides called epitopes, that are presented on MHC class I or II molecules to cytotoxic and helper T cells, respectively.
Three parameters are essential for a therapeutics vaccine to generate potent anti-tumor immunity:
- stimulate multi-epitopic cytotoxic T cell-mediated immunity
CTLs specific for different epitopes will increase the destruction of cancer cells within a heterogeneous tumor mass, and help prevent the outgrowth of antigen-loss variants (tumor immune escape)
- induce Th cells
Th cells are involved in the maintenance of long-lasting cellular immunity, and their tumor infiltration is an essential step in the recruitment and function of CD8+ CTLs.
- promote immunological memory
Immunological memory is essential to protect against tumor relapse.
Amal is proposing a novel cancer vaccine platform that combines these 3 parameters into a single, novel proprietary cancer vaccine construct.