Vaccines, therapeutic

Kosten TR, Biegel D Therapeutic vaccines for substance dependence. Expert Rev... 

Puls RL, Emery S (2006) Therapeutic vaccination against HIV current progress and future possibilities, Clin Sci (Lond) 110 59-71... 

Direct entry of alumina adjuvants through the skin may occur by the use of therapeutic vaccines, with a resultant transient uptake of aluminium in the brain (Redhead et al., 1992). The injection of talc (magnesium silicate)-containing drugs intended for oral consumption has been shown to induce progressive pulmonary fibrosis in drug abusers (Pare etal., 1989). 

Although, these capabilities can be directed to multiple products to target different markets (chemicals, agriculture, protein pharmaceuticals, and prophylactic and therapeutic vaccines) their activities are currently focused to the Health Sector. Within these markets, they are focused on specific high-value opportunities. 

Sela, M., Arnon, R., and Schechter, B. 2002. Therapeutic vaccines realities of today and hopes for the future. Drug Discovery Today 7(12), 664-673. 

Guidance for Industry Considerations for Developmental Toxicity Studies for Preventive and Therapeutic Vaccines for Infectious Disease Indications. U.S. Department of Health and Human Services, Food and Drug Administration Center for Biologies Evaluation and... 

CpG ODNs are also effective as vaccine adjuvants to enhance adaptive TH1 cellular immune responses.104 In mice, CpG ODNs can trigger strong TH1 responses,105 enhancing the number and function of tumor-specific Cytotoxic T lymphocytes (CTLs) and IFN-y secreting T cells.106 This has resulted in therapeutic vaccines in mouse tumor models where no other approach has shown comparable efficacy, even with large (1 cm) established tumors.107 108 Even without a vaccine, CpG ODNs can induce CD8+ T cell-mediated regression of established tumors with durable memory responses.109... 

Bluestone, J.A. and Tang, Q., Therapeutic vaccination using CD4+ CD25+ antigen-specific regulatory T cells, PNAS, 101(Suppl. 2), 14622, 2004. 

Bousquet J, Lockey R, Mailing HJ, Alvarez-Cuesta E, Canonica GW, Chapman MD, et al Allergen immunotherapy therapeutic vaccines for allergic diseases. World Health Organization. American Academy of Allergy, Asthma and Immunology. 

Larche M, Wraith DC Peptide-based therapeutic vaccines for allergic and autoimmune diseases. Nat Med 2005 11 S69-S76. 

Nicolau C, et al. A liposome-based therapeutic vaccine against beta-amyloid plaques on the pancreas of transgenic NORBA mice. Proc Natl Acad Sci USA 2002 99 2332. 

Our laboratory uses a mouse model to study preventative and therapeutic vaccination strategies for human papilloma virus (HPV)-associated tumors. For preventative vaccination studies, six- to eight-week-old female C57BL/6 mice are injected subcutaneously with LPDI on days 0 and 5 and are challenged on day 10 with a subcutaneous injection of 10 E7-expressing TC-1 tumor cells with tumor growth measured three times weekly. 

Marks MJ, Grady SR, Collins AC (1993) Downregulation of nicotinic receptor function after chronic nicotine infusion, J Pharmacol Exp Ther 266 1268-1276 Maurer P, Jennings GT, Willers J, Rohner F, Lindman Y, Roubicek K, Renner WA, Muller P, Bachmann MF (2005) A therapeutic vaccine for nicotine dependence preclinical efficacy, and Phase I safety and immunogenicity. Eur J Immunol 35 2031-2040 Mayo-Smith ME (1998) Management of alcohol intoxication and withdrawal. Principles of addiction medicine, 2nd edn. American Society of Addiction Medicine, Chevy Chase, MD, pp 431 40... 

FDA (2006) Guidance for industry considerations for developmental toxicity studies for preventive and therapeutic vaccines for infectious disease indications, http //www.fda.gov/ ohrms/DOCKETS/98fr/E6-1998. htm. Accessed 16 Sept 2011... 

S. Kinloch-de Loes (2004). Role of therapeutic vaccines in the control of HIV-l. J. Antimicrob. 

Schwartz, M., Protective autoimmunity as a T-cell response to central nervous system trauma prospects for therapeutic vaccines. Prog Neurobiol, 2001. 65(5) 489-96. 

The CBER website on September 24, 2001, included a 12-page, 194-document list of guidance documents spanning blood, therapeutics, vaccines, gene therapy, allergen-ics, tissue, and devices (see www.fda.gov/cber/guidelines.htm, accessed July 2003). 

Therapeutic vaccines were tested in BALB/c mice bearing TA3-Ha mammary carcinoma. The treatment consisted of 4 subcutaneous injections, at 3-6 days intervals, of Detox [a commercial preparation of cell wall skeletons from Mycobacterium phlei and non-toxic monophosphoryl lipid A from Salmonella minnesota (S. minnesota) in squalane oil and Tween 80 from Ribi Immunochemical research, Montana, USA] mixed with Thomsen-Friedenreich (TF) antigen coupled with KLH (Keyhole Limpet Hemocyanin) performed 5 days after the tumor cell injection. This vaccination achieved the survival of 25 % of the mice. Pretreatment of mice with cyclophosphamide in order to inhibit any suppressive response, increased survival to 50 % when the treatment began 5 days after tumor cell injection, and to 90 % when the treatment began 2 days after tumor cell injection. Both antibody as well as delayed-... 

Several trials of therapeutic vaccination used the adjuvant property of lipid A to enhance the vaccination efficacy against human tumors, which are often considered as weakly immunogenic, or even tolerogenic. 

The first trials of therapeutic vaccination against cancer using lipid A as adjuvant were performed on melanoma patients with 0.25 ml Detox. The composition of commercial vaccines used as therapeutic vaccines in humans is given in Table 2. Some trials used a pretreatment with 300... 

Table 2. Composition of commercial vaccines used as therapeutic vaccines in cancer patients.

Trials of therapeutic vaccination against prostate cancer used OncoVax-P (Jenner Biotherapies, Inc, San Ramon, California). OncoVax-P consists of 200 pg monophosphoryl lipid A (similar to that used in Detox) added to 1 ml liposomes and 100 pg PSA (prostate-specific antigen). Patients received injections by different routes (intramuscular, intravenous or subcutaneous) according to the trial, with or without GM-CSF, IL-2 or BCG and cyclophosphamide pretreatment. No serious side effects were seen. DTH and antibody responses were achieved. Vaccination increased the PSA-reactive T cell frequency as determined by IFN-y secretion, but no toxicity against PSA-expressing target cells was detected. The most effective strategy could not be determined, and no conclusion about the clinical efficacy of the treatment was possible [214,215],... 

The phase I and phase II trials of therapeutic vaccines (Table 3.) show a weak toxicity of lipids A, furthermore they show a stimulation of the acquired antitumoral immune response. CTL responses correlate better than antibody responses to clinical outcomes, in agreement with current concepts of antitumor immunity. Phase m trials are now necessary to determine the effective protocol. 

Table 3. List of clinical trials performed with lipids A as adjuvant of therapeutic vaccines administered to cancer patients.

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