Dendritic Cell Info

7/27/2019 Dendritic Cell Info

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DENVAXTM- DENDRITIC CELL THERAPYCustomized Cell-based Cancer Immunotherapy

DENVAXTM

Dendritic Cell Therapy

ICT

Nurturing Cel ls for Lives

INSTITUTE OF CELLULAR THERAPIES PVT LTD


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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


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What is Denvax?

The Denvax is dendritic cell-based cancer

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.

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.

What is the best way to treat relapse?

Cancer treatment modalities like surgical

resection, chemotherapy and/or radiation are

mostly ineffective in controlling the

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

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.

FACTSABOUTDENVAX

Denvaxdelaysdiseaseprogressionandimprovessurvival

Denvaxcanbegivenaloneorincombinationwithothermodalitiesofcancertreatment

Dendriticcelltherapycomesunderthefourthmodalityofcancertreatment,calledImmunotherapy;theotherthreearesurgery,

radiationandchemotherapy Denvaxgivenconcurrentlywithchemotherapyhelpsinalleviatingtheadverseeffectsofthechemotherapy

Denvaxarepatientsownmononuclearcellsmanipulatedintocancer-fightingdendriticcells;thusthereisnograftversushost

reaction,norchancesofacuteordelayedtypehypersensitivity

Denvaxiseasytomanufactureandadminister,duetoCellNuteTM,atransportmediumdevelopedbyICT

CellNuteTMhelpstopreserveandkeepthecellsviablefor19hours,underdesiredconditions

PatientsneednotvisitICTLab,theirbloodcanbecollectedinCellNuteTMandtransportedtoICTinthespecifiedtimeframe

BestresponderstoDenvaxarepatientswhohavecompletedconventionaltherapybutareinthevulnerablehighrelapsegroup


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STEP 1To manufacture a single dose of

DENVAXTM

, a fresh sample ofperipheral blood (20-40 ml inamount as per the TLC count) ofthe patient is collected in

CellNute

TM

medium provided byICT Lab Services.

The day blood is drawn isconsidered Day 1 of the protocol.

STEP 4

The mature dendritic cells are

harvested on Day 8 to be re-infused into the same patient.

The dendritic cell preparation,called Denvax, is administeredintravenously into the patient asan infusion, in 100 ml Dextrose

Normal Saline (DNS) in twentyminutes.

STEP 2

Peripheral blood mononuclear

(CD14+) cells are isolated andcultured in cytokines along withthe desired nutritional media.

STEP 3

These cells transform into the

immature dendritic cells. Formaturation, these cells areexposed to cancerous antigen onDay 6 of blood drawl.

Exposure of DCs to cancerousantigen leads to maturation ofdendritic cells and these matureDCs release various interleukins(specifically IL 12).

Cancerous antigens are bits of protein required for maturation of dendriticcells. This cancerous antigen may be extracted from either source:

a) The patient's Wax Embedded Tissue: tumor tissue preserved in wax forbiopsy examination for further studies;

b) Formalin Fixed Tissue: patients tumor tissue preserved in formalin at thetime of surgery for further studies;

c) Fresh FNA Tissue: fresh sample of tumor tissue derived from Fine NeedleAspiration.

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 antigensare used for dendritic cell maturation. The non-self antigens are derivedfrom 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.


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FAQs

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 cancercells, 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). Theactivated immune system is then able to circulate throughout the body anddestroy the cancer cells.

What happens to the immune system incancer?

In cancer, the immune system fails; cells of the

immune system fail to recognize the cancer cells. Theimmune system doesn't "see" tumors as dangerous

or foreign, and doesn't mount a strong attack against

them. Another reason tumors may not stimulate animmune 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. Numerousresearches now prove that this defect in the immune system can

be corrected outside the body (ex vivo technology). Denvax isdendritic cell therapy, which involves the extraction ofmononuclear (CD14+) cells from the patient's own blood,

transformation of these cells into cancer-fighting dendritic cellsand giving back to the patient.

How is Denvax prepared?

Mononuclear (CD14+) cells are extracted from

the patient's peripheral blood. These cells arecultured, exposed to maturation stimuli and

then re-infused into the same patient on the8th day of blood collection.

What kind of cancers can be treatedby 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.

At what cancer stage should a patient considerDendritic 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 thepatient's tumor cells?

Dendritic cells should recognize the patient's tumor cells and

target them once inside the body. But before that they mustundergo 'maturation'. For this the dendritic cells are exposed

to tumor antigen-self or non-self.

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 are the side effects ofDenvax?

There are minimal side effects.Some patients may experience

mild-moderate grade fever aftervaccine administration lasting 24-48 hours. Some may experiencelethargy/weakness for few days.

What are the contraindications toDenvax?

There are no contraindications to this therapy.


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www.dendriticcellresearch.com

Institute of Cellular Therapies

The Institute of Cellular Therapies (ICT) is the firstand only to offer customized dendritic cell therapyDenvax in India.

ICT Mission

To provide the highest quality of cell therapy atlowest prices, to make the treatment affordable

to a large number of patients.

To individualize each treatment plan andprovide comprehensive treatment in cancer tohelp them overcome their disease.

To help patients achieve complete remissionand prevent relapses by initiating treatment atthe right time, when tumor load is minimal.

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Email :info@dendrit iccellresearch.com

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