UAB 9405 
March 16, 1994 
PAGE -2 
1.0 SPECIFIC AIMS 
In patients with metastatic colorectal cancer, to; 
1.1 Characterize the immune response to carcinoembryonic antigen (CEA) after 
single immunization with a polynucleotide vaccine composed of the plasmid 
DNA of CEA. 
1.2 Characterize the immune response to CEA after three repetitive doses of the CEA 
polynucleotide vaccine. 
1.3 Characterize the toxic or adverse effects associated with single and repetitive 
administration of the CEA polynucleotide vaccine given over a dose range of 0.1 - 
1 .0 mg (single dose) and 0.9 - 3.0 mg (total dose) in a multi-dose regimen. 
2.0 BACKGROUND AND RATIONALE 
2.1 Humans are able to generate an immune response to potential tumor 
relevant antigens following immunization with tumor vaccines. 
There is a long history of clinical trials using various tumor preparations or 
extracts to immunize cancer patients. In general, these have represented rather 
crude attempts at active specific immunotherapy with poorly defined immunogens 
and less than optimal monitoring assays. These problems reflected the state-of- 
the-art in human tumor immunology and not a shortcoming of the clinical 
investigators. Despite these problems, some patients had clinical evidence of anti- 
tumor effects. More recently, several vaccine trials have provided more definitive 
evidence of vaccine-induced anti-tumor responses. Several examples involve 
malignant melanoma studies (1,2,3). The studies by Mastrangelo’s group (1,4) 
have utilized autologous, enzyme disassociated, irradiated tumor cells plus BCG 
to several sites three days following bolus cytoxan. Immunizations were repeated 
Q4 weeks with observed regression of metastatic tumor sites and evidence of 
delayed hypersensitivity skin test reactivity to autologous tumor cells. Mitchell’s 
group (2,5) has immunized metastatic melanoma patients with allogeneic 
melanoma cell line lysates in DETOX (adjuvant) given weekly times 4 and week 
6. Patients developed evidence for delayed hypersensitivity to the immumzing 
lysate and cytolytic T cell precursors to one of the two original allogeneic 
melanoma cell lines they used “cold inhibition” studies to address issues of 
specificity. Objective tumor responses were reported in 4 of 25 (2) and 5 of 17 
patients (5). Bystryn’s group (3,6,7) has immunized low tumor burden melanoma 
patients with a vaccine prepared from material shed into the supemate of four 
different allogeneic melanoma cell lines plus alum (adjuvant) with evidence for 
cellular (6) and humoral response (7) to components of the vaccine and some 
degree of efficacy (3). 
Recombinant DNA Research, Volume 19 
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