By Matthew Willett

Progenics Pharmaceuticals Inc. said it has created human monoclonal antibodies that target prostate-specific membrane antigen. The company developed the antibodies in partnership with Cytogen Corp. using Abgenix Inc.'s XenoMouse technology.

Tarrytown, N.Y.-based Progenics also told researchers at the annual meeting of the American Association of Cancer Research in New Orleans that its joint venture with Princeton, N.J.-based Cytogen, the PSMA Development Co. LLC, entered a collaboration with Abgenix, of Fremont, Calif., for the XenoMouse technology.

Terms of that collaboration were undisclosed.

The collaboration aims to develop human monoclonal antibodies in three forms: a naked antibody, antibodies linked to toxins and radiolabeled antibodies, and company representatives said clinical trials in prostate cancer patients are expected to begin next year.

The antibodies are designed to target and destroy cells with abundantly expressed prostate-specific membrane antigen.

The joint venture also will pursue a parallel program toward the development of therapeutic vaccines that target prostate-specific membrane antigen and stimulate a patient's immune system response to eradicate the cancer.

A prostate cancer vaccine currently in late-stage preclinical development could be advanced to clinical trials later this year, Progenics said.

The AACR meeting will end today. In other news from the meeting:

¿ AVAX Technologies Inc., of Kansas City, Mo., presented data that showed the timing of an "induction" dose of vaccine is critical to achieve maximum immunological and clinical response. Partial-outcome analysis of a 214-patient study indicated that patients with bulky regional lymph node metastases treated with cyclophosphamide and the company's M-Vax responded better to an induction dose of M-Vax five to seven days prior to receiving cyclophosphamide than patients who received the induction dose concurrent to cyclophosphamide administration. The five-year survival rate of the 124 patients given M-Vax prior to cyclophosphamide administration was 55 percent, compared to 33 percent in the 70 patients who received both therapies at the same time.

¿ Celgene Corp., of Warren, N.J., presented data that demonstrated its IMiD class of drugs showed anticancer and anti-inflammatory activity in preclinical studies. Celgene researchers also presented data on the anti-proliferative activity of its selective estrogen receptor modulator under development for treatment of ovarian cancer. Data indicated two IMiD drugs enhanced expression of CD69 by 64 percent and 54 percent. The results suggested the IMiDs increase the expression of CD69 through enhancing production of interleukin-2 by T cells.

¿ Cell Therapeutics Inc., of Seattle, said studies in animal models showed that PG-TXL has superior antitumor activity in human colon cancer than Taxol. PG-TXL links paclitaxel, the active ingredient in Taxol, to a biodegradable polyglutamate polymer. Data suggested that PG-TXL enters cells preferentially and releases paclitaxel, unaffected by chemotherapy exporter pumps associated with Taxol resistance.

¿ EntreMed Inc., of Rockville, Md., released data from a clinical trial and two preclinical studies of Endostatin. The clinical data indicated daily administered Endostatin's pharmacokinetics are linear and consistent at all doses. Preclinical data demonstrated the validity of using Endostatin when administering the breast cancer chemotherapeutic adriamycin. Further preclinical data indicated that a comparison of recombinant human and murine Endostatin revealed that endothelial cells of each species responded to its own Endostatin with a greater affinity than cross-species response.

¿ Genta Inc., of Berkeley Heights, N.J., announced publication of three studies on the cancer-related activity of Bcl-2 protein, the target of Genta's lead antisense compound, Genasense. The studies showed that a high level of Bcl-2 was linked to resistance to radiation treatment in prostate cancer cells, and that Bcl-xL antisense decreased levels of Bcl-xL in prostate cancer cells. Those cells with reduced levels of Bcl-xL, however, were more resistant to chemotherapy. A final study found that vascular endothelial growth factor stimulates production of Bcl-2, which functions as a survival, or anti-apoptosis, factor, as well as interleukin-8, a protein that induces angiogenesis.

¿ ILEX Oncology Inc., of San Antonio, announced results of a study that indicated human turnstatin-5 (turn-5) effectively inhibits tumor angiogenesis. Preclinical model studies indicated the endogenous protein derived from a collagen fragment is at least 10 times more effective than human endostatin at equal dosage.

¿ ImClone Systems Inc., of New York, said preclinical findings indicated its monoclonal antibodies DC101, which targets mouse vascular endothelial growth factor receptor-2, and IMC-1C11, which targets human VEGF-2 (the KDR receptor), show anticancer activity in an human xenograft model of leukemia. Findings suggest that blocking both endothelial cell and tumor cell VEGF receptor pathways is more effective than blocking either pathway alone. Data showed that leukemia-inoculated mice treated with both monoclonal antibodies had long-term remissions without any evidence of disease or metastasis beyond 200 days. In separate news, ImClone presented preclinical findings from a study of its anti-Flt-1 monoclonal antibody indicating the antibody has anti-angiogenic and antitumor activity in a human xenograft tumor model.

¿ Vical Inc., of San Diego, released positive safety and immunogenicity results from the Phase I/II trial of Vaxid, a naked DNA vaccine for low-grade, non-Hodgkin's B-cell lymphoma. Vical said the vaccine was safe and efficacious, and that it generated both a cellular and humoral immune response.

¿ Vion Pharmaceuticals Inc., of New Haven, Conn., presented posters on the therapeutic anticancer protein delivery ability of TAPET vectors. TAPET-CD, which contains the gene E. coli cytosine deaminase, effectively converted 5-fluorocytosine into the anticancer agent 5-fluorouracil, and significantly inhibited the growth of subcutaneously implanted colon tumors, the company said. Further, a single intravenous injection of TAPET-CD in tumor-bearing mice produced a distribution of TAPET-CD in the tumor about 1,000-fold higher than distribution in normal tissue. Vion also said that derivatives of its lead TAPET candidate, VNP20009, that were modified to express and secrete anti-angiogenic peptides did not show lowered tumor-targeting properties, indicating that VNP20009 can be used to deliver anti-angiogenic peptides. n

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