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Dendritic Cell Based Cancer Immunotherapy

Dr. Jamal A. Khan, MBBS MD Immuno Oncologist & Director Institute Of Cellular Therapies Noida

ICT Mission
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; To provide the highest quality of cell therapy at lowest prices, to make the treatment affordable to a large number of patients.

Obtained his masters from Aligarh Muslim University. Had been a researcher and teaching faculty at Aligarh Muslim University. Set up his clinic at Noida in 2005, and began his work in Cancer Immunotherapy. Set up ICT along with his wife Dr. Sharmin Yaqin in 2007.

Dr. Khan also developed a method to collect and store the patients blood for long hours preserving their viability for 19 hours. This nutritional medium is called CellNute, used to collect blood for patients who are distantly located. Dr. Khan is also working in diabetes using mesenchymal stem cells derived from the cord blood as a trial therapy. Till date, Dr. Khan has treated over a thousand five hundred patients suffering from various types of solid tumors, in different stages of the disease. Dr. Khan chaired scientific session on Cancer Immunotherapy in World Cancer Congress, Geneva in August 2008. Dr. Khan is a pioneer in cancer immunotherapy in India, with over seven years of exclusive clinical experience in dendritic cell therapy. His work on dendritic cell therapy in treating cancer is unparalleled in India.

Group of appreciable amount of cells behaving independent of normal check mechanisms.

Revolution in Cancer Therapy

1850

Historically, surgery was the only treatment for Cancer.

1896
1942

Emil Grubbe was possibly the first American physician to use x-rays to treat cancer.

Sydney Farber started giving drugs by vein and is now known as The Father Of Chemotherapy.

1972

Ralph Marvin Steinman discovered the Dendritic Cell and its role in adaptive cancer immunotherapy.

Dendritic cell therapy is a new modality of cancer treatment. It helps in building specific anti-cancer immunity. The dendritic cells are master cells of immune system. On activation of dendritic cells, both arms of immune system, namely humoral and cellular, get energised against cancer antigens.

An elderly male doctor by profession diagnosed with GBM with sarcomatoid component, operated in 2009.

On 15th day of surgery he received his first dose of DENVAX. Received 6 doses every three weeks and is free of recurrence till date.

44 years old female came with the history of repeat surgeries in 2005. The recent one was done for abdominal wall metastasis. She had earlier received chemotherapy & radiation.

Started receiving DENVAX and has complete resolution of disease confirmed by PET-CT in 2007.

Cancer survivor in 2013

THE WEEK MAGAZINE


AUGUST 11, 2012

An 85 year old lady in London diagnosed of CBD cancer operated in May, 2011 (Whipples) Due to comorbidity, was not given chemotherapy Opted for DENVAX and is free of recurrence in 2012 ( PET CT )

Normal cell

++

Mutated cell

++
Disintegrates Suicidal genes

Mutated cell

++
Disintegrates Suicidal genes Fails

Before five divisions

++
Disintegrates Suicidal genes Fails

Before five divisions CD 14+

CD 83/86+ Dendritic Cells

++
Disintegrates Suicidal genes Fails

Before five divisions CD 14+

CD 83/86+ Dendritic Cells

Nave T cell

++
Disintegrates Suicidal genes Fails

Before five divisions CD 14+

CD 83/86+ Dendritic Cells

CD 4+ CD 8+

Nave T cell

Committed T cell

++
Disintegrates Suicidal genes Fails

Before five divisions CD 14+

Robust cellular immunology generated CD 83/86+ Dendritic Cells 3000-5000 T cells/hr For 2-3 weeks

Nave T cell

Committed T cell

Harvest Of DC After 8 Days Of Culture

Chemotherapy helps in rebuilding immunity against cancer

How it works -Exposes internal Epitopes of cancer cell to immune cells

Chemotherapy / Surgery Leads To Unravelling Of :-

External Epitopes

Internal Epitopes

Configurational Epitopes

Structural Epitopes

It Could Be Permanent Or Short Lived !

No patient would like to go for therapy when his oncologist says, YOU ARE NOW OKAY & THERE IS NO EVIDENCE OF THE DISEASE.

Patients who opt for DC are of advanced stages.

The Only Way Is To Prove

DENVAX works in advanced stages too and fulfills recist criteria.

Disturbed Microenvironment Of Tumor Bed

Dr Rakesh Jains Contribution


DIRECTOR EDWIN L STEELE LABORATORY, HARVARD MEDICAL SCHOOL

Tumor microenvironment is disturbed and needs redressal. Blood flow is abnormal due to abnormal microcapillaries in tumor bed. Matrix around tumor has dense fibrin hampering immune cell penetration.

Addition Of Bevacuzimab And Losartan


Bevacuzimab anti vegf , antibody in low doses normalizes the vasculature and maintains normal blood flow.

Losartan restores matrix by clearing excessive fibrin meshwork and helps increase T-Cells invasion.

Revised Treatment Protocol


For Terminally Ill Patients :-

Day 1.

Bevacuzimab

Day 1 - 7 Losartan Day 8.


Repeat

DENVAX Every 15 days

Report 23/06/2011
The band like enhancing lesions along the follia, nodular enhancing lesions in B/L occipital and left frontal lobes along tectal plate are seen as before with more homogenous and intense enhancement with evidence of meningeal enhancement as before.

Report 02/09/2012
No abnormal enhancing parenchymal/meningeal lesion to suggest residual/recurrent mass.

No abnormal enhancement along the spinal cord or caudaequina roots.

References
1. Hanahan D, Weinberg RA. The hallmark of cancer. Cell 2000;100:57 2. Kang Y,Siegel PM, Shu W, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003,3:537. 3. Janeway CA, Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002;20:197. 4. Diefenbach A, Raulet DH. The innate immune responses to tumors and its role in the induction of T-cell immunity. Immunol Rev 2002;188:9. 5. Wu J, Lanier LL Natural killer cells and cancer. Adv Cancer Res 2003;90:127. 6. Lanzavecchia A, Sallusto F. Regulation of T cell immunity by dendritic cells. Cell 2001;106203. 7. Davis MM, Krogsgaard M, Huppa JB, et al. Dynamics of cell surface molecules during T cell recognition. Annu RevBiochem 2003;72:717. 8.Fonteneau JF, Larsson M, Bhardwaj N. Interaction between dead cells and dendritic cells in the induction of antiviral CTL responses. CurrOpinImmunolo 2002; 14:471.

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