ICT

Nurturing Cells for Lives

DENVAX
Dendritic Cell Therapy

TM

DENVAXTM- DENDRITIC CELL THERAPY

Customized Cell-based Cancer Immunotherapy

INSTITUTE OF CELLULAR THERAPIES PVT LTD

Dendritic Cells (DCs) are the key ANTIGEN PRESENTING CELLS (APCs) of the immune system. They are the cells that INITIATE, DIRECT and REGULATE the immune responses.

What are Dendritic cells and how are they useful in fighting against cancer cells?
Dendritic cells considered the pacemakers of the immune system, were originally identified by Steinman and his colleagues in the early seventies. They are crucial to the presentation of peptides and proteins to B and T lymphocytes and are the key antigens presenting cells. They are critical for the induction of T cell responses resulting in cell-mediated immunity. It is the T cell receptors on the T lymphocytes which recognize fragments of antigens bound to molecules of the major histocompatibility complex (MHC) on the surfaces of APCs (dendritic cells). The peptide binding proteins, which are of types I and II, interact with and stimulate cytotoxic T lymphocytes (CTLs) and T helper cells. The antigens from a cancer cell or virus infected cell, on entry into the APC, are processed, spliced into peptides and then re-expressed on the cell surface linked to MHC proteins. This results in generation of CTLs which recognize and destroy cells which express the antigen. The T helper cells which when activated in turn have profound immunoregulatory effects. Therefore, DCs play a key role in host defenses and a crucial role in anti-cancer immune responses

Picture Courtesy: National Cancer Institute, USA

What is Denvax?
The Denvax is dendritic cell-based cancer

What is the best way to treat relapse?

Cancer mostly treatment ineffective modalities in like surgical the

immunotherapy for solid cancers in various stages of disease. It is autologous treatment, which involves patients own mononuclear cells transformed into cancer-specific dendritic cells. Designed to be specific, Denvax targets only the cancer cells without harming the healthy ones. It is safe and effective and works best to prevent relapse and recurrences, the major cause of mortality and morbidity in cancer. Denvax helps in correcting the failed immune surveillance and teaches the immune system to recognize and kill the cancer cells.

resection, chemotherapy and/or radiation are controlling micrometastasis. Micrometastases are single tumor cells or clusters of cells shed by solid cancers and disseminated in various organs of the body. Micrometastases have a pronounced clinical effect, are hard to detect and can be the starting point of recurrence of cancer. Denvax targets the micrometastasis and

destroys the disseminated cancer cells, thereby preventing its development, slowing the spread of cancer and improving the life expectancy.

Under what treatment modality does Why do cancers relapse?

A cancer relapse occurs because in spite of the best efforts to get rid of cancer, some cancer cells are left behind. These cancer cells remain dormant for a period of time, but eventually they continue to multiply resulting in the recurrence or relapse.

Denvax fall?
Denvax is autologous cancer cell immunotherapy. It is also called dendritic cell therapy, cancer vaccine therapy, active-specific immunotherapy, customized therapy, and biological therapy.

FACTS ABOUT DENVAX

Denvax delays disease progression and improves survival Denvax can be given alone or in combination with other modalities of cancer treatment Dendritic cell therapy comes under the fourth modality of cancer treatment, called Immunotherapy; the other three are surgery, radiation and chemotherapy Denvax given concurrently with chemotherapy helps in alleviating the adverse effects of the chemotherapy Denvax are patients own mononuclear cells manipulated into cancer-fighting dendritic cells; thus there is no graft versus host reaction, nor chances of acute or delayed type hypersensitivity TM Denvax is easy to manufacture and administer, due to CellNute , a transport medium developed by ICT TM CellNute helps to preserve and keep the cells viable for 19 hours, under desired conditions TM Patients need not visit ICT Lab, their blood can be collected in CellNute and transported to ICT in the specified time frame Best responders to Denvax are patients who have completed conventional therapy but are in the vulnerable high relapse group

STEP 1
To manufacture a single dose of TM DENVAX , a fresh sample of peripheral blood (20-40 ml in amount as per the TLC count) of the patient is collected in TM CellNute medium provided by ICT Lab Services. The day blood is drawn is considered Day 1 of the protocol.

STEP 2
Peripheral blood mononuclear (CD14+) cells are isolated and cultured in cytokines along with the desired nutritional media.

STEP 3
These cells transform into the immature dendritic cells. For maturation, these cells are exposed to cancerous antigen on Day 6 of blood drawl. Exposure of DCs to cancerous antigen leads to maturation of dendritic cells and these mature DCs release various interleukins (specifically IL 12).

STEP 4
The mature dendritic cells are harvested on Day 8 to be reinfused into the same patient. The dendritic cell preparation, called Denvax, is administered intravenously into the patient as an infusion, in 100 ml Dextrose Normal Saline (DNS) in twenty minutes.

Cancerous antigens are bits of protein required for maturation of dendritic cells. This cancerous antigen may be extracted from either source: a) The patient's Wax Embedded Tissue: tumor tissue preserved in wax for biopsy examination for further studies; b) Formalin Fixed Tissue: patients tumor tissue preserved in formalin at the time of surgery for further studies; c) Fresh FNA Tissue: fresh sample of tumor tissue derived from Fine Needle Aspiration. The cancerous antigens derived from patient's own tumor tissue are called Tumor Associated Antigens, or TAAs. In cases where self-tumor antigens are not available, non-self tumor antigens are used for dendritic cell maturation. The non-self antigens are derived from different sources, similar in nature, and called Tumor Specific Antigens, or TSAs.

DENVAX is also prepared by collecting a greater number of CD14+ cells by apheresis procedure. This allows for a 'one-time' cell collection for multiple dosages. APHERESIS is a cell collection device that helps to collect a large number of desired cell population (CD14+ cells in this case) without having to undergo multiple blood drawl procedures. This saves on travel costs as well as time. Once a DENVAX is prepared by Apheresis method, it can be stored under optimal conditions at ICT and timely dosages can be administered to the patient, as per the treatment protocol. DENVAX prepared by this method is many-fold potent as Apheresis allows for collection of greater number of purified cell population. The COBE Spectra Apheresis System is a cell collection device by CaridianBCT. It is a device which is cleared both by FDA as well as European Medical Device Directive, for mononuclear cell and peripheral blood stem cell collection.

What are Dendritic cells and how are they useful?

Dendritic cells are blood cells present in every person's bloodstream. They function as an immune cell but are present in small numbers. They identify cancer cells, process them into bits, and jumpstart the immune response by bringing the foreign substance to the attention of the rest of the immune system (T cells). The activated immune system is then able to circulate throughout the body and destroy the cancer cells.

What is Denvax (Dendritic cell therapy)?

Cancer occurs because the immune system has failed. Numerous researches now prove that this defect in the immune system can be corrected outside the body (ex vivo technology). Denvax is dendritic cell therapy, which involves the extraction of mononuclear (CD14+) cells from the patient's own blood, transformation of these cells into cancer-fighting dendritic cells and giving back to the patient.

FAQs
What happens to the immune system in cancer?
In cancer, the immune system fails; cells of the immune system fail to recognize the cancer cells. The immune system doesn't "see" tumors as dangerous or foreign, and doesn't mount a strong attack against them. Another reason tumors may not stimulate an immune response is that the cancer cells develop ways to escape the immune system.

How is Denvax prepared?

Mononuclear (CD14+) cells are extracted from the patient's peripheral blood. These cells are cultured, exposed to maturation stimuli and then re-infused into the same patient on the 8th day of blood collection.

Who will benefit most from the therapy?

Dendritic cell therapy works best in patients: who opt early during the disease progression; who opt immediately after surgery, when tumor load is minimal.

What kind of cancers can be treated by Denvax?

This includes solid tumors mainly, including cancers of the breast, bone, brain, bladder, gastrointestinal tract, head & neck, pancreatic, gallbladder, liver, renal, lung, lymphoma, multiple myeloma, ovarian, pancreatic, prostate, and testicular.

What are the side effects of Denvax?

There are minimal side effects. Some patients may experience mild-moderate grade fever after vaccine administration lasting 2448 hours. Some may experience lethargy/weakness for few days.

At what cancer stage should a patient consider Dendritic Cell therapy?

A patient may consider DC therapy when: the patient is free of disease but at a risk of recurrence palliation is required patient requires immune-therapy in addition to ongoing chemo/radiation therapy

How are Dendritic cells made to recognize the patient's tumor cells?
Dendritic cells should recognize the patient's tumor cells and target them once inside the body. But before that they must undergo 'maturation'. For this the dendritic cells are exposed to tumor antigen-self or non-self.

What are the contraindications to Denvax?

There are no contraindications to this therapy.

Institute of Cellular Therapies

The Institute of Cellular Therapies (ICT) is the first and only to offer customized dendritic cell therapy . in India. Denvax ICT Mission To provide the highest quality of cell therapy at lowest prices, to make the treatment affordable to a large number of patients. To individualize each treatment plan and provide comprehensive treatment in cancer to help them overcome their disease. To help patients achieve complete remission and prevent relapses by initiating treatment at the right time, when tumor load is minimal.

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