Therapeutic vaccines are meant to combat existing diseases using a patient’s own immune defences, unlike traditional vaccines which offer protection against infections before they occur.

Stimulating patients’ own immune defences

Cellular response specific for tumour cells

The main goal of a therapeutic cancer vaccine is to generate a cellular immune response including activation of killer T cells (also called cytotoxic T lymphocytes) specific for the tumour cells. In order to achieve a potent immune response, the vaccine must contain molecules called antigens that are also present in the tumour and that need to be delivered to Antigen Presenting Cells (APCs) especially dendritic cells (DCs), to allow anti-tumour immunity to be initiated.

Presentation by MHC class I and MHC class II molecules on APCs allows activation of two classes of T cells, CD8+ cytotoxic T lymphocytes (CTLs) and CD4+ helper T (Th) cells, respectively.

The CTLs will exert their cytotoxic function for killing tumoral cells and Th cells will promote immunological memory necessary for a long-lasting anti-tumour immune response.

New class of standardised therapeutic vaccines

Despite a generally high level of safety, therapeutic vaccines display only low-to-moderate efficacy and require extensive preparation. Our aim is to develop a new class of competitive therapeutic vaccines, based on ease of preparation & administration, efficacy and price that could be administered to a broad range of patients.

It is expected that combinations with immune-modulators will increase significantly the level, the strength and the duration of an immune response after vaccination. Our development programmes therefore include evaluation studies of different combinations with immune-modulators.

Focus on oncology

We have developed a powerful and versatile immunisation technology called KISIMA® whose range of potential applications goes way beyond the cancer vaccines we currently focus on in our development pipeline.

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 which includes all the treatments where the immune system is modulated, such as passive immunotherapies, immuno-modulators, adoptive transfers and cancer vaccines. Recently, the use of immunotherapies has greatly modified the global landscape of cancer treatment.

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Effective cancer therapies

If targeted therapies, generally small molecules or antibodies, have demonstrated the interest of blocking some specific molecular mechanisms of cancer cells to impact cancer progression, the use of immunotherapies has revolutionised the entire cancer treatment approach.

Indeed, training, stimulating and strengthening human body defences to fight against abnormal cell growth has provided the hope for safer treatments having a prolonged effect to reduce cancer burden.

Our aim is to offer effective cancer therapies by complementing existing standards of care and by working in synergy with current immune-checkpoints inhibitors.

Therapeutic cancer vaccines are administered to cancer patients in order to strengthen the capability of their immune system to recognise and kill tumour cells.

In order to allow cancer immunity to be initiated and for the induction of a potent tumour specific immune response, a therapeutic vaccine needs to fulfil the three parameters below.

AMAL’s KISIMA^® immunisation platform combines all these into a single, novel proprietary cancer vaccine construct and is highly adaptable for a large spectrum of antigens and/or indications.

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1

Stimulate multi-epitopic CD8+ CTL-mediated immunity

CTLs specific for different epitopes will increase the destruction of cancer cells within a heterogeneous tumour mass, and help prevent the outgrowth of antigen-loss variants (tumour immune escape)

2

INDUCE CD4+ HELPER T (TH) CELLS

Th cells are involved in the maintenance of long-lasting cellular immunity, as well as supporting tumour infiltration, which is an essential step in the recruitment and function of CD8+ CTLs.

3

PROMOTE IMMUNOLOGICAL MEMORY

Immunological memory is essential to protect against tumour relapse.

Induction of an immune response

A vaccine contains molecules called antigens which are also present in the tumour and that need to be delivered to Antigen Presenting Cells (APCs) especially dendritic cells (DCs), to allow cancer immunity to be initiated.

These cells process an antigen into peptides called epitopes, that are presented on MHC class I or II molecules to CD8+ cytotoxic T lymphocytes (CTLs) and CD4+ helper T (Th) cells, respectively.

In addition, to become fully activated, beside antigen recognition, T cells require a second signal, the co-stimulatory signal, which is antigen non-specific and is provided by the interaction between co-stimulatory molecules expressed on the surface of APCs and the T cell. The TLR-agonist of KISIMA^® boost the expression of these co-stimulatory molecules by APCs.

Thus, activated antigen specific T cells proliferate, migrate and infiltrate the tumour leading to the killing of tumoral cells.