More information

DENVAX™

Customised Cell-based Cancer Immunotherapy

DENVAX DENDRITIC CELL THERAPY

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 70’s. They are crucial to the presentation of peptides and proteins to B and T lymphocytes and are the key antigens presenting cells and 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 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 to the APC, are processed, spliced into peptides and then re-expressed on the surface linked to MHC proteins. This results in generation of CTLs which recognize and destroy cells which express this antigen. The T helper cells when activated in turn have profound immunoregulatory effects.

DCs therefore play a key role in host defenses and a crucial role in anti-cancer immune responses.

What is Denvax™?

It is dendritic cell-based cancer immunotherapy for solid cancers in various stages of disease. It is autologous treatment, which involves patient’s own mononuclear cells transformed into cancer-specific dendritic cells.

Designed to be specific, Denvax™ targets only the cancer cells without harming 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 to correct the failed immune surveillance and teaches the immune system to recognize and kill the cancer cells

Why do cancers relapse?

Cancer relapse occurs in spite of the best efforts of prevention because 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 of disease or relapse.

What is the best way to treat relapse?

Cancer treatment modalities such as surgical resection, chemotherapy and/or radiation are mostly ineffective in 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 life expectancy.

Under what treatment modality does 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 to alleviate the adverse effects of chemotherapy.

• Denvax™ is made with patient’s own mononuclear cells that are manipulated into cancer-fighting dendritic cells, thus there is no graft versus host reaction, nor chances of acute or delayed type hypersensitivity.

• Denvax™ is easy to manufacture and administer due to CellNute™, a transport medium developed by Institute of Cellular Therapies (ICT).

• CellNute™ helps to preserve and keep the cells viable for 19 hours, under desired conditions.

• Patients need not visit the ICT lab as their blood can be collected in CellNute™ and transported to ICT within 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 Denvax™, a fresh sample of peripheral blood (20-40 ml in amount as per the TLC count) of the patient is collected in CellNute™ medium provided by ICT Lab Services. The day blood is drawn is considered Day 1 of the protocol. Blood samples can be drawn at NCI Cancer Hospital in Nilai.

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

Step 3
The cells transform into the immature dentritic cells. For maturation, these cells are exposed to cancerous antigen on Day 8 of blood draw. Exposure of DCs to cancerous antigenleads to maturation of dendritic cells and these mature DCs release various interleukina (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 100ml 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: Patient’s tumor tissue preserved in formalin at 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

FREQUENTLY ASKED QUESTIONS

What happens to the immune system in cancer?

In cancer, the immune system fails; cells of the immune system fails 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.

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, transforming the cells into cancer fighting “dendritic cells” and administering back into the patient.

What are dendritic cells and how are they useful?

Dendritic cells are blood cells present in everyone’s bloodstream, functioning as an immune cell but are present in small numbers. They identify cancer cells, processing it into bits and jumpstart the immune response by introducing its foreign substance to the rest of the immune system which in turn circulates throughout the body and destroys cancer cells in the process.

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 and neck, pancreatic, gallbladder, liver, renal, lung, lymphoma, multiple myeloma, ovarian, pancreatic, prostate and testicular.

Who will benefit most from the therapy?

Dendritic cells works best in patients:
• Who opt early during disease progression;
• Who opt immediately after surgery, when tumor load is minimal

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 risk of recurrence
• palliation is required
• patient requires immune-therapy in addition to ongoing chemo/radiation therapy

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.

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 side effects of Denvax™?

There are minimal side effects. Some patients may experience mild to moderate grade fever after vaccine administration lasting 24 – 28 hours. Some may experience lethargy/weakness for a few days.

What are the contraindications to Denvax™?

There are no contraindications to this therapy.