The development of therapeutic cancer vaccines has proven to be a rocky, winding, pothole-filled, mostly uphill road, as companies like Dendreon Corp., Antigenics Inc., the late CancerVax Corp. and many others can attest.

But Neogenix Oncology Inc. is applying knowledge from the cancer vaccine field to the development of monoclonal antibodies. Specifically, the Great Neck, N.Y.-based start-up has created chimeric monoclonal antibodies targeting immunogenic tumor-associated antigens (TAAs) isolated from some of the first cancer vaccines ever tested.

While some scientists have lamented that the epitopes used in cancer vaccines today may not be sufficiently immunogenic, Neogenix's TAAs allow the antibodies to "kill the cancer rather than just slowing it down," said Neogenix cofounder and CFO Peter Gordon. One of the antibodies in development has been shown to kill 58.2 +/- 3.2 percent of the cells in an H441 lung cancer cell line and 40.3 +/- 0.2 percent of the cells in an H596 lung cancer cell line, comparable to the 54.8 +/- 5.9 percent and 44.0 +/- 3.9 percent, respectively, killed by an active control antibody.

But while the active control antibody theoretically would kill both cancerous and healthy cells, Neogenix's TAAs are specific to cancerous cells. That differentiates them from existing monoclonal antibodies like Rituxan (rituximab, Genentech Inc. and Biogen Idec Inc.), which targets the CD20 antigen found on both cancerous and healthy b cells.

Neogenix's TAAs date back to the late 1970s and early 1980s, when a team led by Ariel Hollinshead, of George Washington University Medical Center, isolated TAAs from the tumors of several cancer patients and created specific active immunotherapeutics. Those early cancer vaccines were tested in clinical trials run by government, academia and hospitals, in which they showed antitumor responses and the ability to prolong survival in a variety of cancers.

In one study, which evaluated 85 patients with Stage I and II squamous cell lung carcinoma, 75 percent of patients treated with the vaccine and CFA adjuvant survived five years, compared to 53 percent of patients on the adjuvant alone and 34 percent of the control patients. Median overall survival was 106 months for the vaccine-treated group (p=0.007), 71 months for the adjuvant-only group and 38 months for the control group.

Yet the vaccines never were commercialized because the FDA had deemed the pooled allogeneic products suitable only for research use. After an attempt at creating antibodies grown in fetal calf serum, the project was shelved temporarily. Then team member Myron Arlen, who spent 20 years at Memorial Sloan-Kettering Cancer Center and co-founded North Shore Surgical Oncology Associates, decided to start a biotech called International BioImmune Systems Inc. (IBS). (See BioWorld Today, May 19, 1997.)

Arlen founded IBS in the 1990s to create antibodies to the TAAs. In 2004, he went on to found Neogenix, where he currently serves as CEO and is overseeing the development of second-generation antibodies. Gordon said Neogenix and IBS have discussed joining forces, but it "didn't work out." He emphasized that none of the Neogenix patents infringe on IBS's intellectual property because Neogenix's antibodies have been "radically redesigned."

Neogenix purchased the frozen patient samples - essentially "25 years worth" of work, Gordon said - from Hollinshead and the other scientists.

The samples contain TAAs in lung, colon, bladder, prostate, brain, breast and ovarian cancers, as well as melanoma.

Neogenix's lead antibody, dubbed NPC-1C, is derived from an immunogenic glycoprotein molecule found on the surface of both pancreatic and colon cancer cells. The company has had three pre-IND meetings with the FDA to discuss plans for a Phase I/II program in pancreatic cancer.

Last month, Neogenix teamed up with contract manufacturer Goodwin Biotechnology Inc., of Plantation, Fla., for process development and manufacturing of NPC-1C. Gordon said that once the FDA has seen the results of purity studies, they will review the investigational new drug application filing. The company hopes to be in the clinic in the first half of 2008.

Beyond NPC-1C, Neogenix is developing antibodies for colon cancer and lung cancer. The company also plans to use its antibodies to develop tests for early stage diagnosis of cancer and, in the long term, to apply the TAAs to cancer vaccines once again.

But for now, the start-up is focusing its limited resources - a staff of seven full-time employees and about $6.5 million in private funds raised to date - on NPC-1C. Gordon said the company is in the process of fund raising again, but will continue to stick to private accredited investors rather than courting venture capitalists or pharmaceutical partners.

"We want to keep control of the science," he said.