Stimulating the immune system to fight cancer.

ECP was originally introduced by Edelson in 1987 (Yale University). ECP is used worlwide in the treatment of cutaneous T-cell lymphoma, autoimmune diseases, transplant rejection, graft-versus-host disease, etc.

Extracorporeal Photopheresis is a therapy that works on a cellular level; using a chemical substance that sensitizes the cells to ultraviolet irradiation. We use a combination of an oral medication with the ultra violet light device accomplishing two important purposes; it activates certain molecules inducing apoptosis (a gentle way of destroying abnormal cells) and it activates the monocytes. The monocytes then convert into dendritic cells, (the cells which initiate immune reactions).In 24 hours we see the evidence of our work. Overnight, the monocytes enter the dendritic cell pathway.

Vaccines target associated antigen are highly antigenic and it maybe target by the immune system.

Mechanism of Action: Upon exposure to UVA light, covalent crosslinking of DNA occurs. This resulting in the proliferative arrest of the treated cells. The passage of mononuclear cells through UV light will convert to mature and educated dendritic cells, Macrophage dendritic cell activation leading to enhanced processing of apoptotic
T-cell antigens and release of pro-inflammatory mediators. Induction of T-cell apoptosis and induction of anticlonotypic by the above processes.

Cells exposed to UVA light may undergo cell-cycle arrest, which Usually occurs at S phase or G-1 S boundary. The cell may repair itself and tolerate the damage before resuming the cell cycle. Or, the cell may die by apoptosis. UV light favors apoptosis.

Immune activation or immune-suppression upon phagocytosis of apoptotic cells is dependent on the maturity of Dendritic Cells; Immature Dendritic Cells induces tolerance, mature Dendritic Cells initiates immune activation.

The combination of Extracorporeal Photopheresis with Dendritic Cells vaccines, plays a central role in the initiation of immune responses, creates the development of novel therapeutic strategies against tumors and other disease.

The generation of an effective T cell-mediated immune response requires the activation of both the cytotoxic (CD8+) and the helper (CD4+) T lymphocyte subsets.

The CD8+ cytotoxic T-lymphocytes are activated by the presence of tumor antigen coupled to an MHC class 1 peptide, synthesized within the cytoplasm of the tumor cell.

Nearly all cells in the body express MHC class 1 antigen. In tumor cells this antigen then binds to the antigen-specific T-cell receptor (TCR) on the CD8+ T-lymphocyte, stimulating T-cell activation.

Full activation of the CD8+ T-lymphocyte into a cytotoxic T-lymphocyte (CTL) capable of tumor cell lysis, however, requires the presence of cytokine as well. This cytokine secretion is provided through CD4+ helper T-cell activation, injection of GM-CSF, combined with tumor antigens in vivo will attract autologous DCs to the immunization site where they would uptake the injected antigens.

In the light of these findings, the combination of extracorporeal photopheresis and immunizations with autologous DCs cultured ex vivo (functionally intact), prepulsed with tumor antigens is a wonderful strategy to elicit a strong immune response in the cancer patient.

Now that we comprehend the mechanism, it is possible to apply this adoptive immunetherapy (Autologous ECP/DC) to poor-prognosis solid tumors or with minimal residual diseases, prolonged survival with good quality of life and without undesirable effects.

In the last few years science has witnessed a massive expansion in the understanding of antigen presenting cells known as dendritic cells. 7

Dendritic Cells (DCs) were first described by Steinmann and Cohn in 1973.  They were first observed in the spleen and peripheral lymph nodes of mice.  Soon, similar cells were found in skin (where they had been previously termed Langerhans cells), Peyer’s patches, and the liver. 8

DCs have the ability to induce primary T-Cell dependent immune response in vitro and in vivo.
This unique feature gives DC’s an important role in controlling immunity. 9

Dendritic cells (DCs) are potent antigen presenting cells (APCs) that possess the ability to stimulate naïve T-cells. They are comprised of a system of leukocytes which are widely distributed in all tissues; especially in those that provide an environmental interface. 10

Immune activation or immunosuppression upon  phagocytosis of apoptotic cells is dependent on the maturity of DC.   That is, while immature DC induces tolerance, mature DC initiates immune activation. 11

Dendritic cells are responsible for identifying pathogens (viruses, fungi, bacteria, malignant cells) and presenting their identifying markers, antigens, to specific T-lymphocytes that then multiply and attack the disease. They are also capable of identifying normal dying cells and to present their antigens to different T-cells that tell the immune system not to attack its own tissues.

This review describes the experience with the development of a novel form of immunotherapy that may represent the first practical and effective means of performing tumor-loaded dendritic cell immunotherapies. This optimizes the quality of life for all people living with cancer and viral infections. Remember: Emotional, spiritual, and mental components of health are as important as the physical. We value listening to the needs of our patients and create services to meet those needs.

This Method is Useful for:

Cancer vaccines are made with dendritic cells (DC´s) which play a crucial role in the initiation of primary immune response and are therefore probably the best support for anti-tumor adoptive immunotherapies. The use of peripheral blood mononuclear cell mobilization with Extracorporeal Photopheresis (ECP) and incubation. This process will induce antigen-specific regulatory T-cells, as alternative strategies for immune therapies.

The last few years science has witnessed a massive expansion in our understanding of antigen presenting cells known as dendritic cells. 13 This unique feature gives DC’s an important role in controlling immunity. DC’s have the ability to induce primary T-Cell dependent immune response in vitro and in vivo. 14 One of the most exciting new areas of dendritic cell research, is the use of these cells for immunotherapies of malignant diseases.

The vaccine works in a way to enhance the immune functions. It is prepared from the patient's own blood, which represents his/her own unique internal environment. The preparation follows procedures that favor the development of antigenic peptides and other immunogenic compounds in the fight against cancer and other immune disorders. Experience has shown that it stimulates formation and activation of macrophages, T-helper cells, and natural killer cells.
DCs play a central role in the initiation of immune response. Creating possibilities for their use in the development of therapeutic strategies against tumors and other diseases. 12

One of the most exciting areas of dendritic cell research, is the use of these cells for immunotherapy of malignant diseases.

Dendritic cells are responsible for identifying pathogens (viruses, fungi, bacteria, malignant cells) and presenting their identifying markers (antigens), specific to T lymphocytes that then multiply and attack the disease. They are also capable of identifying normal dying cells and presenting their antigens to different T cells that tell the immune system not to attack its own tissues.

The Instituto de Investigaciones Biomedicas (IIB) is a leader in the field of cancer immunotherapies since 1999 by using novel therapies such as extracorporeal photopheresis (ECP) and other cancer vaccines in the treatment of malignancies and degenerative diseases.

Induction and specific anti-tumor immunity by active immunization has been the aim of researchers for decades.  Recent research has been directed at identifying and defining tumor-specific and tumor-associated antigens.

Experience has shown that the effectiveness of any vaccine is enhanced when it is administered within a comprehensive biological treatment program, including a special nutrition program.