Researchers at Lidak Pharmaceuticals are developing "virtual"tumor cells for their potential use as cancer vaccines. Theydesign these artificial particles by coating red blood cell-sizesilica beads with the isolated plasma membranes of tumor cells-- a process that results in what Lidak of San Diego has termeda large multivalent immunogen (LMI).
According to preclinical data presented Saturday at the FirstInternational Conference on Engineered Vaccines for Cancerand AIDS in San Francisco, these tumor antigen-coated beadsare capable of significantly enhancing the ability of cytotoxic Tlymphocytes (CTLs) to attack living tumor cells of like origin. Infact, the purpose of the LMI is to stimulate and increase thiscell-mediated immune response.
Lidak senior scientist Philip Morrow, who presented thepreclinical data, said the LMI approach works both in animalmodels and in the test tube. The animal model involvesimmunizing mice by injecting them intraperitoneally withmurine tumor cells. Immediately thereafter or simultaneouslythe mice then receive beads coated with membranes from thesame tumor cell line -- injected intraperitoneally,intravenously or subcutaneously, Morrow explained.
"Seven to 10 days later, we examine the peritoneal cavity andmeasure the amount of tumor cell growth," he said. As controls,the researchers used "irrelevant" coated beads (e.g., withmouse serum) or no beads at all. "With the membrane-coatedbeads we see a significant reduction in the number of tumorcells," Morrow told BioWorld.
Altogether Lidak scientists have immunized mice with four orfive different tumor cell lines, he added. As furtherverification, the researchers have analyzed in vitro the killingability of lymphocytes from such immunized mice.
Lidak has picked melanoma as its first human target for anLMI vaccine. The trial design will involve immunizing patientswith beads coated with membrane preps from a humanmelanoma cell line, then measuring their melanoma-specificCTL response over time from blood samples drawn weekly. Thepatients' progress will also be monitored clinically, Morrowexplained. "The two usually correlate," he said.
Unanswered details of the vaccination methodology remain tobe worked out. For instance, the scientists still don't have adefinitive picture of either the beads' half-life or their specificlocation in the body. Also to come are further studies in miceon the long-term effects of the immunization procedure as wellas the effect of immunization on tumors that have alreadybecome well-established.
There are some preliminary animal data on both, however. Forone, the researchers have found that when they injected thetumor antigen-coated beads into mice 11 days after the micehad been given live tumor cells, there was an "excellentregression of the tumor mass and prolonged survival of themice," said Morrow. For this experiment, the scientists easedthe tumor-killing task by giving the mice a shot of the drugcyclophosphamide four days before the beads.
"We didn't think our beads alone would work with anestablished tumor," Morrow told BioWorld. Cyclophosphamidetreatment will be used in the human melanoma trial as well, headded. That trial will be conducted in collaboration withMalcolm Mitchell at the University of Southern CaliforniaSchool of Medicine.
-- Jennifer Van Brunt Senior Editor
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