Technology

Common concerns associated with the use of live Listeria and how Advaxis addresses them

Toxic effects
Listeria is gram-positive and therefore, free of endotoxins found in gram negative bacteria like Salmonella. Innate immunity alone is sufficient to clear infections by Advaxis' vectors in mice. These vectors are attenuated compared to the wild-type Listeria; the lethal dose in mice is ten thousand times to one hundred thousand times higher.
Listeria related deaths in natural infections
Reported Listeria outbreak cases of death are usually due to meningitis or sepsis in elderly or immunocompromised individuals. Because Listeria is an infrequent cause of disease and first causes a flu-like syndrome in healthy individuals, recognition and initiation of proper treatment of the infection is often delayed. Because of close monitoring and known medical history of Listeria vaccine recipient�s, untoward effects can be quickly and effectively treated. We have shown that out of 11 common antibiotics tested, 9 of them stop Listeria infection at low doses and do so without stopping the therapeutic immune response once it has been initiated. Thus, in the event of a problem, the Listeria infection can be rapidly terminated without a negative effect on the treatment.
Pregnant women in the third trimester will be excluded from vaccination as they are from other live vaccines. Strongly immunocompromised individuals will not be eligible for Listeria based immunotherapy, which would not make scientific sense in this patient group. Most cancer patients are not severely immunocompromised until the final stages of disease.
Adverse events
In therapeutic doses we have found that the side effects associated with Listeria administration are similar to the side effects associated with most immuno-therapies, and consist of a flu-like syndrome comprised of fever, chills, nausea and so forth. These effects respond to aspirin-like drugs and we suggest the administration of such drugs prior to the administration of Listeria to minimize or eliminate such side effects.
Therapeutic vs Prophylactic vaccines
Lovaxin C is a therapeutic vaccine, which means it is intended as a treatment for women who already have cervical cancer. The currently approved HPV vaccine, Gardasil, and the one in development, Cervarix, are focusing on prophylactic vaccination against HPV infection before it occurs. These vaccines do not work in already infected women, as their vaccines prevent infection but do not cure an infection which already exists. These manufacturers claim they would like to eradicate cervical cancer, however to do so they must treat all women at risk before they are sexually exposed to the agent. HPV is the most common STD in the US, which makes this task difficult; and even if they were successful this treatment outreach they would not address today�s population currently affected. Thus, even if prophylactic vaccines are successful, given the decades it would take to treat all of the women at risk, the prevalence of HPV in the general population, and the 20-40 year lead time it takes to manifest disease; there is likely 50 years (or more) before during which therapy for cervical cancer will be required.
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