TREATMENT ISSUES, Volume 6, Number 5; The Gay Men's Health Crisis Newsletter of Experimental Therapies - May/June 1992
Michael Becker

Cellector Therapy

The "Cellector" is a device made by Applied Immune Science (AIS) that stimulates immune CD8 cells (same as T8 or suppressor cells). It may be useful in treating AIDS, Kaposi's Sarcoma (KS), and other HIV-related opportunistic infections and cancers. AIS, a California-based biotechnology company, is attempting to treat disease by "harvesting" or stimulating a particular class of CD8 cells, known as cytotoxic or "killer" cells from blood or bone marrow. The device removes the blood from the patient and isolates the cytotoxic CD8 cells with Interleukin-2 (IL-2), a natural immune booster. The cells are then reintroduced into the patient's body approximately two weeks later. IL-2 is a genetically manufactured protein found naturally in the body. It is believed to stimulate the rapid growth and activity of CD8 cells.

The procedure has been tested in patients with AIDS in Phase I trials in Pittsburgh and Miami. Approximately twelve patients received between five to seven treatments in escalating doses of IL-2 on a monthly basis. Published reports about the Cellector have not included mention of the infusion of low-dose IL-2 two-to-three days before the re-introduction of the treated blood. IL-2 is thought to maintain the biological activity of the reintroduced cells. Once the stimulated cytotoxic or "killer" CD8 cells are reintroduced into the body, they attack infected or malignant body cells. Theoretically, this process should help destroy not only HIV-infected cells but also otherwise damaged or malignant cells. This therapy theoretically provides immune protection against opportunistic infections such as toxoplasmosis, cytomegalovirus (CMV), and Pneumocystis carinii pneumonia (PCP).

Early Human Trial Results

While AIS has not yet published results from the Phase I trials, it has reported that the Cellector causes no adverse reactions or toxicities. Initial concerns about an inflammatory response or other serious side effects seem to be unfounded.

No patient involved in the trial experienced any opportunistic infections while receiving Cellector therapy. Two patients with chronic wasting had significant weight gain; three patients with hairy leukoplakia had a relief in symptoms, and two patients with KS (each of whom had "failed" chemotherapy) had significant reductions in their lesions. The phase I trials were not originally designed to measure efficacy or changes in surrogate markers, so these findings must be interpreted cautiously.

Phase II Trials

Based on the phase I results, AIS is now developing a phase II trial for the treatment of KS. The trial plan will soon be submitted to the FDA for approval. Projections have the trials starting in late spring 1992 in San Francisco and Miami. AIS is focusing on the treatment of KS in order to prove efficacy and obtain prompt FDA approval for the therapy with appropriate speed. The company has no current plans to develop phase II trials for AIDS or HIV infection itself.

AIS entered a joint venture with Caremark, an affiliate of Baxter Health Care Corp., to secure the cell-therapy and laboratory services necessary for this complicated treatment. Caremark is building a facility in San Francisco which will provide support for the phase II trials. Questions about dosing and the clinical benefit from low-dose IL-2 remain to be answered. If the therapy is effective, it is most likely that repetitive lifelong treatments will be required.

Push For Development

The Treatment and Data Committee of ACT UP/New York has called upon the National Institute of Allergy and Infectious Diseases (NIAID) to investigate the Cellector and, if warranted, to sponsor broader trials for AIDS and HIV infection. NIAID scientists have preliminarily suggested to Treatment Issues that cells activated by the Cellector demonstrated predominantly non specific activity and, therefore, may have minimal anti-HIV activity. Moreover, they report no effect on absolute CD4 or CD8 counts and question whether the benefits from the therapy (particularly in treating KS) were, in fact, due to the IL-2 infusion rather than the Cellector process itself. Notably, KS has been known to respond to cytokines such as IL-2.

Other CD-8 Therapies

Researchers are also working on the possibility of expanding HIV-CD8 cell therapy. The CD-8 cells are removed and given time to proliferate before they are re-infused into the HIV-infected individual. It is hoped that the HIV-specific CD8 cells, (cells that react to certain proteins produced by HIV) will destroy HIV-infected cells and result in significant clinical benefit to the patient.

A small, 14-person, federally funded clinical trial will test both the safety and activity of reinfusing HIV-specific CD8 cells. According to the researcher designing the trial, a vigorous response may protect HIV-infected asymptomatic individuals from progressing to symptomatic disease. This researcher told Treatment Issues that HIV-specific CD8 cells have been isolated from HIV-infected individuals and stimulated. Test tube studies show that they have rigorous activity against HIV-infected cells. The chief concern of this researcher is that HIV may be able to mutate so that the CD8 cells would not be able to continue to recognize it as a target. This trial will not require IL-2 infusions, and patients will be allowed to remain on anti-viral therapy.

Gene Therapy

The Recombinant Advisory Committee of the NIH recently gave permission to the Targeted Genetic Corporation to begin clinical trials involving the implementation of genetically-modified cytotoxic CD8 cells into patients with AIDS. It is hoped that these altered cells will kill HIV-infected cells or AIDS-related cancer cells. Several other companies are developing similar techniques. In general, the procedure involves implanting specific genetic material into a viral envelope. Theoretically, the viral genetic material in the envelope will then "infect" targeted cells and introduce the new material into the patient's own cells. It is hoped that the new material will provide enhanced immune function.

The initial gene therapy trials are intended to examine safety and to determine whether the genetic material can be implanted into the targeted cells in the body. Because we do not know the potential risks of this procedure, the newly implanted genes will contain a "suicide gene" which will make it possible to kill the altered cells if the procedure proves harmful.

Conclusion

It is important to note that many biotechnology companies operate with minimal capital and revenues. Often these companies depend on the favorable opinion of the stock market to fund their operations. Therefore, promising reports and public statements issued by companies should be read critically. For example, AIS was in the middle of an important public financing at the time it made public disclosures about the preliminary Cellector results. Some officials from NIAID suggest that the company may have been engaging in public hype. Reports must be carefully reviewed and verified.

Nevertheless, it is encouraging to see new treatment for AIDS enter clinical trials. These therapies, like HIV-vaccine therapies, seek to stimulate a patient's own immune system to act against HIV. However, hopes must not be raised prematurely. The basis for these treatments may shed light on newer theories that suggest AIDS may be the end result of a long period of over-stimulation of the immune system. Finally, the financial cost and ultimate feasibility of these treatments remain to be addressed.

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