PROSPECTIVE ANALYSIS OF DENDRITIC CELL(DC)THERAPY IN CANCER PATIENTS

1. 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 LLK *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 he had a biopsy done by his primary ENT surgeon at Normah Kuching who detected a poorly differentiated squamous cell from the parotid. All this was happening in the presence of a negative for 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 to have adjuvant chemotherapy with Cisplatin and 5FU which he turned down for the second time. He wanted to try on Denvax therapy. 10 weeks post therapy he noted a large swelling on the jaw and this progressed . He had 2 infusions of Denvax that was uneventful. Dendritic Cell therapy was well tolerated with hardly any side effects. The efficacy was more pronounced in patients with minimal disease. CONCLUSION 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