GI-4000 With Adoptive Transfer in Pancreatic Cancer

Inclusion Criteria:

Adult patients with untreated, locally advanced pancreatic adenocarcinoma that expresses a GI-4000 related k-ras oncoprotein.

1. Histologically-confirmed pancreatic adenocarcinoma that expresses one of the GI-4000-related k-ras oncoproteins (G12V, G12C, G12D, Q61L, or Q61R)
2. Locally advanced disease, (stages I-III, i.e no evidence of metastasis outside the pancreas and its regional lymph nodes). Preferred subjects for entry into the study are those with borderline resectable disease, as defined by:

   * tumor that encases a short segment of the hepatic artery without extension to the celiac axis and that is amenable to resection and reconstruction, OR
   * tumor that abuts the superior mesenteric artery and that involves \<180 degrees of the circumference of the artery, OR
   * short-segment occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option available for vascular reconstruction because the veins are normal above and below the area of tumor involvement.
3. Age \>18 years
4. ECOG performance status 0 or 1
5. Normal organ and bone marrow function as defined by:

   Absolute neutrophil count \> 1,500/μl Platelets \> 100,000/μl AST(SGOT)/ALT(SGPT)\< 2.5 X institutional upper limit of normal Bilirubin \< 2.0 mg/dL unless due to bile duct blockage by tumor Creatinine \< 1.5 x ULN
6. A biliary stent 9F or biliary bypass before treatment, if tumor-related biliary obstruction is present
7. The ability to sustain adequate hydration and nutrition (\>1500 cal/d) by oral intake or access for supplemental enteral feeding (nasoenteral tube, feeding jejunostomy or PEG)
8. Patients must have measurable disease by radiographic imaging, as defined by 1 lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20 mm with conventional techniques or 10 mm with spiral CT scanning. Marker elevation alone is insufficient for entry.
9. Ability to understand and the willingness to sign a written informed consent documents.
10. Adequate venous or catheter access and ability to tolerate apheresis.

Exclusion Criteria:

1. Tumor metastatic to peritoneum, liver or other organs
2. Tumor that is clearly resectable for curative intent
3. Prior chemotherapy, radiation therapy, targeted therapy, or immunotherapy for pancreatic cancer.
4. Receipt of any other investigational agents within 30 days prior to screening
5. Known HIV positive
6. A major surgical procedure or significant traumatic injury within 28 days prior to anticipated initiation of chemotherapy, an anticipated major surgical procedure during the course of the study, or a minor surgical procedure (laparoscopy, fine needle aspiration, or core biopsy) within 7 days of anticipated initiation of chemotherapy.
7. Serious non-healing wounds, ulcers, or bone fractures
8. Pregnancy or ongoing breast-feeding, as chemotherapy may pose substantial risk to the fetus/infant.
9. Patients whose treatment plan would require treating \>50% of the liver to a dose greater than 30 Gy or treating \> 50% of the total kidney volume to a dose greater than 18 Gy
10. Positive scratch test (immediate hypersensitivity, IgE mediated) to S. cerevisiae.
11. Active autoimmune disease requiring immunosuppressive therapy