Dendritic Cell Based Cancer Immunotherapy

Dr. Jamal A. Khan, MBBS MD

Immuno Oncologist & DirectorInstitute Of Cellular TherapiesNoida

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.

Founder – Dr Jamal A. Khan

• 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 patient’s 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.

Founder – Dr Jamal A. Khan

What is Cancer ?

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

•Historically, surgery was the only treatment for Cancer.1850

•Emil Grubbe was possibly the first American physician to use x-rays to treat cancer.1896

•Sydney Farber started giving drugs by vein and is now known as “The Father Of Chemotherapy”. 1942• Ralph Marvin Steinman discovered

the Dendritic Cell and its role in adaptive cancer immunotherapy.1972

Revolution in Cancer Therapy

What is Dendritic Cell Therapy ?

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.

• 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.

G B M ( WHO Grade IV )

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

Cancer survivor in 2013

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

Metastatic Pancreas Cancer

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.

THE WEEK MAGAZINE AUGUST 11, 2012

Opted for DENVAX and is free of recurrence in 2012 ( PET CT )

Due to comorbidity, was not given chemotherapy

Common Bile Duct Cancer

An 85 year old lady in London diagnosed of CBD cancer – operated in May, 2011 (Whipples)

Normal cell

Mutated cell

+ +

Mutated cell

+ +

Suicidal genes

Disintegrates

+ +

Suicidal genes

Disintegrates

Before five divisions

Fails

+ +

Suicidal genes

Disintegrates

Before five divisions

Fails

CD 83/86+Dendritic Cells

CD 14+

+ +

Suicidal genes

Disintegrates

Before five divisions

Fails

CD 83/86+Dendritic Cells

Naïve T cell

CD 14+

+ +

Suicidal genes

Disintegrates

Before five divisions

Fails

CD 83/86+Dendritic Cells

Naïve T cell Committed T cell

CD 4+CD 8+

CD 14+

+ +

Suicidal genes

Disintegrates

Before five divisions

Fails

CD 83/86+Dendritic Cells

Naïve T cell Committed T cell

Robust cellular immunology

generated

3000-5000 T cells/hrFor 2-3 weeks

CD 14+

Collect In Cellnute Medium

Transfer to lab within 19 hrs at

room temperature

Method – 1.Peripheral Blood Collection

Method – 2. DENVAX Production

Isolation Of Monocytes ( CD 14 Cells )

Harvest Of DC After 8 Days Of

Culture

Exposure Of Immature DC To Antigens

Culture In RPMI 1640/GM-CSF/IL-4

Medium

Method – 3. DENVAX Infussion

Distribution in 6 Doses

Each Dose Given IV By Mixing In 100ml DNS At

20 Days Interval

Role Of Chemotherapy

Chemotherapy helps in rebuilding immunity against

cancer

How it works -Exposes internal Epitopes of cancer

cell to immune cells

External Epitopes

Internal Epitopes

Configurational Epitopes

Structural Epitopes

Revival Of Immunology

Chemotherapy / Surgery Leads To Unravelling Of :-

Unravelling Of Internal Epitopes

On Achieving CR

It Could Be Permanent Or Short – Lived !

Dilemma To Accept The Therapy at Right Stage

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 Jain’s ContributionDIRECTOR 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 :-

•BevacuzimabDay 1.

•LosartanDay 1 - 7

•DENVAXDay 8.• Every 15 daysRepeat

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;106-203.

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.

THANK YOU