Transcript Prospective analysis of dendritic cell (DC) therapy in cancer patients`.

PROSPECTIVE ANALYSIS OF DENDRITIC
CELL(DC)THERAPY IN CANCER PATIENTS
AP233
Kananathan.R*,Khan Jamal**
*NCI Hospital,Nilai Negeri Sembilan, Malaysia
**Institute of Cellular Therapy(ICT) ,Noida,India
INTRODUCTION
Cancer is caused by mutations.
Familial
environmental
unknown etiology.
During cancer development, self-cells become non-self cells. Mutating cells acquire a shield mechanism for evading immune attack.
They may hide their antigenic nature by topographic shield or produce IL-10 for negative chemotaxis or develop an unknown hidden mechanism to evade their arrest. Once the
cancer cells start proliferating, the immune mechanisms become so ineffective, that it actually starts contributing towards cancer proliferation. At this stage, cancer develops
rapidly and profoundly. Otherwise cancer growth may become slower or delayed if immune system is still able to check it irregularly. The deranged immune system can be
corrected passively by chemotherapy and/or surgery. If it happens this way, cancer patients become cancer survivors, or otherwise, cancer returns with vengeance making itself
more resistant to chemotherapeutic drugs used earlier. Normal anti-cancer immunology can be enhanced in laboratory as well. The peripheral blood mononuclear cells are
isolated from peripheral blood and cultured with specific cytokines for changing their morphology to dendritic cells.
The dendritic cells are given a basic information of cancer type, by adding tumor associated antigens (TAA) and tumor specific antigens (TSA) to the culture plates. First described
by the late Professor Ralph Steinmen( picture Nobel Prize in Medicine 2011 ) in the late 1980 dendritic cells are now found to have essential roles in cancer therrapy Dendritic
cells recognize the antigen feedback and respond by producing specific antigenic peptides (representation) on their surfaces. These mature dendritic cells are re-infused to the
same patient after eight days of culture for generating specific anti-cancer immunity. After infusion, these dendritic cells along with specific cytokines are carried to various lymph
nodes and station themselves in these lymph nodes. They start their physiological action on naïve T cells. Upon physiological contact with dendrites of DC, T cells become
committed in the vicinity of dendritic cells. Each dendritic cell has the potential to mature to about 3000-5000 T cells/hour. Dendritic cell survives on an average of 3 weeks to
months, and during this period it is able to selectively transform trillions of T cells.
The robust anticancer immunology doesn’t allow new malignant cells to grow and effectively stops or delays tumor progression. Dendritic cells leading to IL-12 and TNF-alpha
generation also generate humoral immunology which results in reducing cachexia.
We have a series of advance cancer patients who used DC therapy in this review.
METHODLOGY
Patients who had advance cancer who have failed ,not suitable or refuse standard therapy were given the option of DC therapy.
Sign an informed consent agreeing to under go the therapy.
Phases I
Bleeding
0.1ml of Heparin is drawn into the syringe. 20ml of fresh blood is drawn .
The drawn blood is poured into CellNute Bottle.
CellNute is a transport medium used to collect and transport blood back to ICT in India by 12hours on the same day.
At ICT ,CD14+ cells are isolated and cultured in cytokines along with desired nutritional media. These cells transform into the
immature dendritic cells .These cells are matured by exposing them to cancerous antigens on Day 6.
Phase II
The matured dendritic cells are harvested on Day 8 to be infused into the same patient.
Intravenous ondenseteron is given prior to Denvax Infusion.
RESULTS
11 patients
5 males and 6 females
Age ranged from 36 to 67years
Cancers
CA Colon(3),Hepatocellular Carcinoma(2),Ca Breast(1),CA Tongue and Nasopharyngeal (1)
CA cholangiocarcinoma(1),CA Cervix(1),CA Endometrium(1),Ca Prostate(1)
Infusions given ranged from open patient passed away 24hours before his first infusion and one patient had
6 infusion.Median is 4 infusion
No adverse event was noted post transfusioan
AGE
SEX
DIAGNOSIS
STAGE
SURGERY
THERAPY
DC THERAPY
OVERALL SURVIVAL
CAA
67
MALE
CA COLON
IV
ANTERIOR RESECTION
FOLFOX
CHEMO RADIOTHERAPY
CRYOTHERAPY
HARVESTING DONE
PATIENT PASSED AWAY 24HOURS
BEFORE INFUSION
22MONTHS
OPT
64
FEMALE
CA COLON
IV
RIGHT HEMICOLECTOMY
FOLFOX WITH CETUXIMAB
FOLFIRI
CAPECITABINE
2 HARVESTING
23MONTHS
CYC
57
MALE
CA COLON
IIIC
OCT 2004
RIGHT HEMICOLECTOMY
JUNE 2009 TOTAL COLECTOMY
OCT 2004
3 HARVESTING
FOLFOX 12 INFUSIONS OVER
6MONTHS AT NCI
JUNE 2009 FOFLFOX,.
RISING CEA ,PET REVEALED
SINGLE PARA AORTIC NODES
,GIVEN RADIOTHERAPY.. REFUSE
FURTHER CHEMO
84MONTHS SINCE PRIMARY DIAGNOSIS ,
30MONTHS POST RECURRENCE.
ALIVE
SJ
41
MALE
CA LIVER
PORTAL HYPERTENSION
CHILD C
III
NIL
SOREFINIB FOR 3MONTHS
ALFA FETOPROTEIN KEPT ON
RISING
2 HARVESTING
ALFAFETOPROTEIN DROPED FROM
480IU/L TO 220IUL
6MONTHS PASSED AWAY AFTER AN
INFECTION ON RETURN FROM INDIA.
LLK
57
FEMALE
CA LIVER
PORTAL HYPERTENSION
CHILDS C
III
NIL
WAS NOT FIT FOR LOCAL
REGIONAL OR SOREFINID
2 HARVESTING
DISEASE PROGRESSED
6MONTHS
DMCH*
53
MALE
CA TONGUE
NASOPHARYNGEAL
IV(June 2008) NOTE BELOW
IV (June
2009)
CONCURRENT CETUXIMAB AND
RADIOTHERAPY IMRT TO
TONGUE
CONCURRENT CHEMORT FOR
NPC
1 HARVESTING
24MONTHS
45
FEMALE
CA CERVIX
IIIB
NIL
CONCURRENT
CHEMORADIOTHERAPY
6CYCLES OF PACLITAXEL AND
CARBOPLATIN
2 HARVESTING
36MONTHS
17MONTHS POST RECURRENCE
FEMALE
CA CHOLONGIO
CARCINOMA
IV
NIL
3LINES OF THERAPY
HIFU
SIRTEX
AIET
2 HARVESTING
30MONTHS
LLK
SAJ
YCC
AR
36
FEMALE
CA LEFT BREAST
TRIPLE NEGATIVE
IIIC
1 LEFT MASTECTOMY WITH
1FAC AND CHEST WALL
2 HARVESTING
82MONTHS SINCE DIAGNOSIS
AXILLARY CLEARENCE
RADIOTHERAPY
48MONTHS POST RECURRENCE
*Remain well till June 2009 when he developed numbness over his right lower face and wasting of his left lower neck muscles. He was examined in France and a CT scan was done that revealed no abnormality and radiotherapy was blamed for this effect. One month later he had left parotid swelling and ENT surgeons at Prince court Medical Centre attributed it to an infection. Finally
LOCAL
EXCISION
he had a biopsy done by his primary ENT surgeon at Normah Kuching who detected a poorly differentiated squamous cell from the parotid.2All
this was happening
in the presence of a negative2forTAXOTERE
tumour at the primary site. He was sent for a PET scan at Singapore General that revealed a large enhancing lesion in the nasopharyngx. He was treated and post therapy he was advised
REpost
EXCISION
3 RADIOTHERAPY
to have adjuvant chemotherapy with Cisplatin and 5FU which he turned down for the second time. He wanted to try on Denvax therapy. 10 3
weeks
therapy he noted a large swelling on the jaw
and this progressed . He had 2 infusions of Denvax that was uneventful.
TCC
39
FEMALE
CA ENDOMETRIUM
IC
TAHBSO AND PELVIC NODE
SAMPLING
INTRA CAVITY BRACHYTHERAPY
2HARVESTING
53MONTHS SINCE DIAGNOSIS
26MONTHS POST RECURRENCE
MM
65
MALE
CA PROSTATE
IV
NIL
HORMONE
PALLIATIVE RADIOTHERAPY
1 HARVESTING
31MONTHS
CONCLUSION
Dendritic Cell therapy was well tolerated with hardly any side effects.
The efficacy was more pronounced in patients with minimal disease.
Presented at the 21st Asian Pacific Cancer Conference
10 to 12th November 2011
Dedicated to Late Dr G Selvaratnam,patients and the staff’s of NCI