HPV Immunotherapy Research

Warts & All
An immunotherapy candidate seeks to address complications from HPV
by Chael Needle

Human papillomavirus (HPV) is the most common sexually transmitted infection, but, according to the CDC, most who are infected never develop symptoms nor health problems. Keep in mind, though: a history of anogenital warts in men and women has been linked to a thirty-fold increase in the risk of anal cancer; and eighty percent of anal cancers have been linked to persistent HPV infection in the anal region. Additionally, those living with HIV are more likely to not only contract HPV but also, if they do, are more likely to develop health complications from a persistent HPV infection compared to those who are HIV-negative.

If you are one of the 79 million Americans who are HPV-infected and have an immune system compromised by HIV, you and your physician should be alert to the possibilities: development of anogenital warts and certain types of cancers.

A new Phase I dose-escalation study is underway, led by John D. Malone, MD, MPH, Head, Clinical Investigations Department, Naval Medical Center San Diego NMCSD), and Research Program Manager, Navy Medicine West, that is looking at the safety of Multikine, an investigational immunotherapy developed by Cel-Sci, in HIV/HPV co-infected men and women with peri-anal warts. The purpose of the study, which started with five participants and may add ten more if no serious adverse events are reported after a set time, is to evaluate the safety and clinical impact of Multikine injections as a treatment of peri-anal warts and assess the compound’s effect on anal intraepithelial dysplasia (AIN).

Researchers, like Dr. Malone, are building on what we know about HPV: “First, there are different kinds, at least 150 different strains of HPV. For a long time, we’ve known that certain strains are much more likely to be associated with cancer and, in particular, with cervical cancer in women,” he notes about the long-established association. “More recently we’ve run into the relationship between rectal warts and that being a predispostion to develop anal cancers, or rectal cancers.” That’s why the study design chose to focus on both the unsightly, contagious warts and AIN, abnormal cells in the rectal area that look to be pre-cancerous.

Peri-anal warts are canaries in the coalmine, sometimes indicating dysplasia, a precursor to cancers. Treat the warts, and one may be able to prevent the cancers. But researchers are also interested in the coal—that is, a potent immune system response that would work to suppress HPV.

The two-fold question of Multikine’s potential mechanism of action is open: Does it work to eradicate warts at a local level, thereby preventing possible progression to dysplasias, or could it also stimulate the immune system response in order to control HPV infection to prevent it from developing into cancer?

If and when safety is established, these research questions about efficacy will be pursued.

This study builds on the promising early results of another Multikine Phase I study at the University of Maryland, which showed that the compound has the ability to clear lesions in HIV/HPV co-infected women with cervical dysplasia and eliminate different strains of HPV. Multikine was also found to be well-tolerated among study participants. The compound is also currently being tested in a global Phase III clinical trial as a potential first-line treatment for advanced primary head and neck cancers, some of which have been associated with HPV infection.

Research interest in cancers has been energized by the fact that many individuals with HIV/AIDS are living longer and facing age-related health conditions. Notes Dr. Malone, who is also credentialed as an Infectious Disease Staff Physician: “The medications have fortunately changed the face of the epidemic, which is great, as now all of us realize [treating someone with HIV is] more like taking care of someone who has diabetes, or heart failure: We’re giving them their medicine and trying to make sure that they have healthy lifestyles; and there’s no reason that they should not live to be very old people. But, as we all age, the usual diseases come up: cancers, heart attacks, and liver problems.”

Having run an HIV/AIDS unit at National Naval Medical Center Bethesda from 1989 to 1994, Dr. Malone knows well the beneficial effects of antiretrovirals as well as having one’s virus suppressed. As a way to prevent cancers from developing, he notes, it’s always good to have your HIV under control. “We certainly know that when HIV infection has high viral loads and low CD4 counts, you’re much more prone to infections, but you are also much more prone to cancers. That was seen in people who developed lymphomas in the early part of the epidemic, before the drugs were around—Kaposi’s sarcoma, and others, and also cervical cancer in women. In the early HIV epidemic, before the drugs were around, cervical cancer killed many women. So, having your virus under control, with this drug or without this drug, is a key piece to long-term health.”

Beyond controlling one’s virus, other ways to potentially prevent HPV-associated cancers include the HPV vaccine, notes Dr. Malone. “Use and acceptance of that HPV vaccine by all individuals should result in significant public health advances. As more people are vaccinated, and women in particular, I think we’re hoping that rates of HPV infection and anal carcinoma will fall.”

As for Multikine, the research team at NMCSD is interested to chart its potential. Says Dr. Malone: “I think it’s a good promising product, and we here at the Naval Medical Center San Diego are looking to advance the medical research and clinical care for all of our patients and many, many people throughout the world. And we’re pleased to participate to make the world a little better.”

Chael Needle is Managing Editor of A&U.