Memopi® is a disruptive technology which re-educates the body’s immunological memory so that the immune system (and particularly T cytotoxic cells) attacks tumor cells by increasing the patients’ specific cytotoxic T response against their cancer.
Treatments using Memopi® aim to stabilize the development of the disease and to extend patients’ life.
The development of innovative treatments such as Memopi®, provides patients who face poor prognosis or therapeutic failure an important, new therapeutic option.
Thousands of epitopes have been studied in Research & Development and were individually optimized to define the best rational choice of a multi-epitopes combination from various tumor antigens. This selection process was drastic and led to identification of 11,722 candidate peptides. Based on the binding to T response receptors, 223 peptides were selected and chemically modified to increase their binding to the receptors. 46 peptides were identified as having a strong capacity of binding to the HLA-A2 or TCR receptors.
The epitopes arise from tumor antigens present in several cancers and are expressed in more than 90% of cancers. They are either overexpressed in the tissues (such as HER2/neu) and are CarcinoEmbryonic Antigens (CEA), or of testicular origin (such as MAGE) or antigens from tumor suppressor gene (such as p53, damaged gene in half of the cancers).
In a second step, based on in vitro and in vivo synergy, 10 epitopes were selected to constitute Tedopi®. These epitopes of different types were optimized (increased affinity to HLA-A2 and to other epitopes, increased affinity to T or TCR receptors) and associated in a single combination including an epitope stimulating T “helper” lymphocytes, also called PADRE.
The synergy of the combined multi-epitopes determined this selection in order to obtain a strong and durable T cytotoxic response.
The T cell (blue cell) ensures immunosurveillance of cancer, if it can recognize cancer cells (green cell) with surface receptors recognized as foreign.
At invasive stage of cancer, the cancer cell foils immunosurveillance by dysregulation of immunosurveillance system in the tumor site, in parallel with a high expression of tumor antigens associated with a strong tumor growth.
9 T epitopes selected and optimized for enhanced HLA -A2 and TCR binding are combined with a T helper epitope (subcutaneous administration with an adjuvant); the epitopes combination will restore immunosurveillance.
The epitopes Injection attracts presenting cells (APC) that express the epitopes on their surface for presentation to immune cells.
An Amplification of messages (cellular messengers called cytokines) is initiated involving T helper.
T cells are becoming T cytotoxic cells, they are informed and armed.
T cells are activated when their TCR will bind to HLA -A2 receptor, strong binding of epitopes to both receptors induces a strong T cytotoxic response.
Armed cytotoxic T cells recognize the tumor antigens on the surface of cancer cells. The cytotoxic T response is specific for epitopes and for tumor antigens they represent.
Cytotoxic T cells specifically destroy cancer cells that express tumor antigens referred.
The OSE technology is unique, it targets 5 tumor antigens at a time. Selected tumor antigens are expressed in several cancers, they have a poor prognosis and are over-expressed in disseminated or invasive stage. NSCLC tumors are heterogeneous but more than 90 % of tumors expresses at least one of the 5 selected tumor antigen or tumoral proteins (CEA, p53, HER- 2 / neu, MAGE -2 and MAGE -3).