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Directly Conjugated Single-Domain VHHs Targeting MHC Class II Prime T-Cell Responses Against Pancreatic Cancer Neoantigens

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Technical Report,30 Sep 2016,29 Sep 2019

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Dana-Farber Cancer Institute Boston United States

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Background Pancreatic cancer is one of the deadliest cancers, with a 5 year survival rate of 5. The exceptionally poor prognosis of this disease can be traced to several factors. Located in a vital region of the body, the majority of primary pancreatic tumors are inoperable and rapidly metastatic. Furthermore, pancreatic cancers are dense, fibrotic masses that preclude adequate drug delivery. Immunotherapy has shown impressive clinical benefit for other cancers, particularly for metastatic melanoma. Since immunotherapy targets the immune system, and not a particular type of cancer, these new drugs were originally hoped to be applicable across all tumor types as a pan-cancer medication. However, pancreatic cancer was among the cancer types in which immunotherapy has largely failed. We propose a novel strategy of using an alpaca single domain antibody against MHC class II to activate CD4 T cells against pancreatic cancer specific neoantigens. T cell activation would occur outside the tumor, in lymph nodes and spleen our hope is that these activated T cells would then infiltrate the pancreatic mass and cause tumor rejection.

Subject Categories:

  • Medicine and Medical Research
  • Biochemistry
  • Pharmacology

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