Summary

Immudel-gp120 was tested in human white blood cells for its ability to eliminate the production of anti-gp120 antibodies. The results imply that Immudel-gp120 specifically and thoroughly eliminates the production of anti-gp120 antibodies, but does not harm the production of antibodies to other foreign proteins. Immudel-gp120 was then tested for side-effects and safety in both human cells and rats. No side effects or safety concerns were observed in either case. Rats and human cells treated with Immudel-gp120 demonstrated no significant difference from control (untreated) rats or cells, even with relative doses many times that of the expected human dose.

Efficacy of Immudel-gp120

Immudel-gp120 was designed to prevent the production of anti-gp120 antibodies, while not impacting the production of antibodies to other foreign proteins. (For an explanation of how anti-gp120 antibodies cause damage to the immune system, see Non-Technical Summary or Autoimmune Model.) Experiments were conducted to determine whether Immudel-gp120 is effective as designed.

In the experiments, samples of normal human white blood cells were grown in petri dishes with different additions to their medium. After an appropriate period, the samples were tested for the presence of human antibodies.

The following table summarizes the findings. Pokeweed mitogen is a foreign protein known to stimulate high antibody responses in B cells.

Additions to Medium and Antibody Levels Observed
	No Immudel-gp120	With Immudel-gp120
No foreign proteins	low background levels	low background levels
With gp120 (done twice)	high levels	low background levels
With pokeweed mitogen	very high levels	lower but still very high levels

Immudel-gp120 showed the ability to reduce the total production of antibody to the same levels observed in the cultures with no foreign proteins. This demonstrated that Immudel-gp120 is effective at reducing antibody response. The fact that the culture treated with Immudel-gp120 had a strong antibody response when stimulated with pokeweed mitogen demonstrates that Immudel-gp120 does not eliminate al B cells. Cells treated with Immudel-gp120 could still mount a strong antibody response against another foreign protein.

These studies imply that Immudel-gp120 specifically and thoroughly eliminates gp120-specific B cells, thereby eliminating the production of anti-gp120 antibodies, but leaving intact those B cells specific to other proteins.

Safety of Immudel-gp120 in Human Cells

Previous compounds of somewhat similar design employed a different toxin which caused vascular leak syndrome, an often fatal syndrome in which the cells of the blood vessels are damaged, causing fluid to leak into lungs and other tissues. Because it uses a different toxin, we expected that Immudel-gp120 would not cause vascular leak syndrome.

To test for vascular leak syndrome, which does not occur in rat models, human blood vessel cells were separately grown with Immudel-gp120, two compounds of known toxicity (DMSO and mitomycin), and with no additions (for vehicle control).

The activity and growth of the cells were then measured using a dye which changes color in the presence of viable cells, but not in the presence of failing or dead cells. The amount of changed dye was then measured for all the samples, indicating the amount of activity and growth/death of the cells.

All five concentrations of Immudel-gp120 showed results similar to the control sample with no additions. In other words, Immudel-gp120 did not cause significant growth inhibition or cytotoxicity to the cells even at the highest concentration, a dose that exceeds the expected human maximum dose by 50-fold. In contrast, the known toxic compounds caused dramatic dose-dependent decrease in cell activity.

We conclude from this study that Immudel-gp120 is unlikely to cause vascular leak syndrome and shows promise for safety in other human applications.

Safety of Immudel-gp120 in Rats

The objective of this study was to determine if Immudel-gp120 causes side-effects or unexpected damage. The study was carried out in rats, which are traditionally used to assess potential toxicity of new drugs.

Six animals, three in each group, received a total equivalent of four or sixteen times the expected human monthly dose of Immudel-gp120. This total dose was administered as two equal injections, one 24 hours after the other. One control animal received equivalent injections of saline, and another received no injections. All animals were euthanized 24 hours after receiving the final dose for post-mortem tissue collection and analysis.

All animals were observed frequently and appeared normal throughout the in-life phase of the study. They did not exhibit any behavioral or outward health abnormalities. No immediate post-dosing reactions were noted after the intravenous injections of Immudel-gp120 or saline. The body weights for each animal were measured before and after the study period. No significant changes in body weight occurred.

Blood from each animal was fully analyzed, including individual serum chemistry, complete blood counts (CBCs), and white blood cell differential counts. All values appeared to be within acceptable limits of normal variability. Values for treated animals did not differ significantly from control animals or from known normal ranges.

Tissues from major organs (brain, heart, liver, kidney, thymus, spleen, lung, lymph nodes, and testes or ovary) were removed and examined by a pathologist for any apparent abnormalities. Only very slight abnormalities were present in the tissues of any of the rats, and the control rat revealed a pattern of slight abnormalities similar to the test rats. The pathologist concluded that no changes could be attributed to treatment with Immudel-gp120.

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