Novel immunotherapy strategy for treatment of pancreatic cancer

DESCRIPTION provided by applicant Pancreatic cancer has the worst prognosis of all cancers and is the fourth leading cause of cancer related deaths in the United States Patients usually present with advanced disease making curative attempts difficult Surgery is the only curative therapy since radiotherapy and chemotherapy remain largely ineffective coupled with undesirable side effects Despite the great excitement over targeted therapies such as kinase inhibitors resistance always arises making them at best debulking agents Further targeted therapies often do not increase long term survival while immunotherapies may Indeed immunotherapy has been shown to overcome resistance A number of active monoclonal antibodies mAb such as Herceptin Erbitux and Rituxan and several others are already approved for treatment of certain cancers However to generate long term sustained anti tumor response mAbs require T cell help There is clinical evidence for mAbs driven T cell immunity IL is a well established cytokine that can potentiate mAbs via improved NK ADCC However in clinical trials IL has shown minimal clinical benefit when administered in combination with mAbs mostly because IL does not stay in circulation for long Dr Wittrup collaborator has been successful in increasing IL PK exposure via Fc or Albumin MSA fusion More importantly we have generated strong preliminary data that Fc MSA IL can potentiate several mAb activities in immune competent mouse models of cancer We have recently patented a unique tMUC antibody designated TAB that reacts strongly with tumor tissue but does not bind to normal epithelia MUC is over expressed in an altered form in more than and pancreatic ductal adenocarcinoma PDA and metastatic lesions respectively In addition we have generated human MUC expressing pancreatic ductal adenocarcinoma model PDA MUC mice Cell lines from these tumors have also been generated and tagged with luciferase for in vivo imaging We hypothesize that TAB Lip MSA IL will be therapeutic and will strongly suppress tumor growth by activating effector CD T cells and recruiting neutrophils and increasing NK cell ADCC Specific Aims are to assess tumor growth and metastasis in response to Lip MSA IL TAB in the spontaneous and orthotopic PDA models using the IVIS imaging system and to assess the immune responses induced by the combination Successful achievement of Phase I STTR will pave the way for a clinical trial The implications from these studies could be far reaching and could lead to an improved therapeutic strategy for pancreatic cancer PUBLIC HEALTH RELEVANCE We propose to develop a therapeutic product for the treatment of pancreatic cancer We will explore if the therapeutic efficacy of a tumor specific antibody can be enhanced when administered in conjunction with a long lasting liposomal MSA IL Data from this study will form the basis for future clinical trials and development of a FDA approved drug for patients with pancreatic cancer