Innovation in Cancer Treatment. Immunotherapy.
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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.
Transcript of Innovation in Cancer Treatment. Immunotherapy.
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
