Harvard University (MA, USA) researchers, led by David Mooney, have described how an implant under the skin could attract and train immune cells to attack and kill tumor cells in a murine model. The findings were published in the November 2009 issue of Science Translational Medicine.
The immune system often fails to recognize cancer cells, although in theory, cancer cells possess many features that make them different from other cells. To date, therapeutic vaccination strategies often involve injecting tumor antigens, in different formulations, in an attempt to train immune cells to recognize the tumor cells better, or even removing immune cells from the body to train them in vitro before infusing them back into the body to fight cancers.
In this new study, the researchers placed an 8 mm plastic implant under the skin of mice that carried tumors. The implant sends out signals that recruit dendritic cells of the immune system. Once inside the implant, these dendritic cells are exposed to tumor proteins, and upon leaving the implant, the trained dendritic cells can target tumor cells better. “Vaccination by this method maintained local and systemic CTL responses for extended periods while inhibiting FoxP3 Treg activity during antigen clearance, resulting in complete regression of distant and established melanoma tumor‘, wrote the authors.
This device is the first ‘cancer vaccine‘ of its kind, according to the authors. “Inserted anywhere under the skin – much like the implantable contraceptives that can be placed in a woman‘s arm – the implants activate an immune response that destroys tumor cells,” commented Mooney.
“This study provides some useful insights into how we can effectively train the immune system to recognize and destroy cancer cells,” said Joanna Owens, science information manager at Cancer Research UK. “The use of an implant to deliver the vaccine is particularly interesting and the results look encouraging, but more research is needed to see if the technology can be scaled up and adapted for use in people.”
For human use, the implant needs little modification, but the tumor-antigen components will need to be changed. The researchers concluded that the findings “provide a template for future vaccine design.”
Sources: Ali OA, Emerich D, Dranoff G, Mooney DJ: In situ regulation of DC subsets and T cells mediates tumor regression in mice. Sci. Transl. Med. DOI: 10.1126/scitranslmed.3000359 (2009) (Epub ahead of print); BBC News: http://news.bbc.co.uk
Researchers from Harvard Medical School (MA, USA), Los Alamos National Laboratory (NM, USA) and the National Institute of Allergy and Infectious Diseases (MD, USA) believe that they have made a discovery that could prove helpful in the fight against HIV-1 transmission in humans.
It is estimated that approximately half of all sexually contracted HIV-1 cases occur when the individual transmitting the virus is newly infected. This is believed to be due to replication of the HIV-1 virus being most intense and peaking during this period.
Currently, vaccines capable of inducing neutralizing antibodies that could offer protection against a variety of HIV-1 isolates are not available. However, research shows that vaccination is capable of inducing HIV-specific T lymphocytes that are able to limit viral replication during primary infection in nonhuman primates.
Rhesus monkeys and SIV are frequently used as models for human HIV infection and HIV is believed to have arisen when SIV crossed the species barrier into humans.
The US researchers immunized rhesus monkeys with vaccine vectors expressing SIV Gag/Pol, both of which are structural proteins found in HIV and SIV. A second group was vaccinated with a control vaccine construct, following which both groups were subject to intravenous challenge with a highly pathogenic SIV quasispecies.
In their findings, detailed in the Journal of Virology, the researchers analyzed the semen viral load of the two groups from samples collected once weekly for 6 weeks and then biweekly for the subsequent 16 weeks.
During the analysis, the researchers discovered that in the control group SIV RNA was detected by day 7 and reached a peak at day 28 postinfection. In the Gag/Pol-vaccinated group, detection of SIV RNA did not occur until day 14. At day 21, semen SIV RNA levels peaked at a lower level than the control group before declining to undetectable levels 6 weeks postinfection and staying that way until the end of the study at day 80.
“The demonstration in the present study of a direct association between vaccination and diminished seminal plasma SIV RNA levels suggests that vaccination may be an effective measure for reducing HIV-1 transmission,” commented the researchers.
This research could be of use in the generation of an altruistic vaccine that could be used to decrease viral load in HIV-1-infected individuals and, thereby, prevent or drastically reduce transmission rates. This technique has therefore been suggested as a possible method of controlling the HIV epidemic in countries where it is most prevalent.
Source: Whitney JB, Luedemann C, Hraber P et al.: T-cell vaccination reduces simian immunodeficiency virus levels in semen. J. Virol. 83(20), 10840–10843 (2009).
LFB Biotechnologies (France) has announced that the EMEA‘s Committee for Orphan Medicinal Products has granted its investigational therapeutic product, LFB-R603, the orphan-drug status. LFB-R603 is currently under a Phase I/II clinical trial for the treatment of chronic lymphocytic leukemia (CLL).
Also known as B-cell CLL, CLL is the most common type of leukemia and accounts for approximately 30% of adult leukemia cases in Europe. In CLL, B-lymphocytes proliferate uncontrollably and do not function properly due to DNA damage; they invade the bone marrow and blood, and interfere with other healthy blood cells. This can result in anemia and/or thrombocytopenia (fall in platelet count) and can cause patients to become immunocompromised and susceptible to infections. Although considered incurable, CLL progresses slowly and most patients survive for several years – sometimes decades – following diagnosis. Currently available treatments focus on controlling symptoms, and range from chemotherapy, radiotherapy and immunotherapy to bone marrow transplantation.
LFB-R603 is a chimeric recombinant monoclonal antibody against CD20, an antigen expressed on the surface of B lymphocytes. LFB-R603 has a specific glycosylation profile that enhances its antibody-dependent cell-mediated cytotoxicity activity against malignant B lymphocytes. This cytotoxicity activity has been demonstrated in in vitro and in vivo preclinical trials, and this new antibody could be more effective than the reference anti-CD20 antibody.
Source: LFB Biotechnologies, France: www.lfb.fr
Results from a Phase IIb trial assessing the efficacy of Lupuzor™ for the treatment of systemic lupus erythematosus (SLE) have demonstrated statistically significant superiority over placebo.
The Phase IIb study was a randomized, double-blind, placebo-controlled, dose-ranging study conducted in 150 patients suffering from SLE. The aim of the trial was to evaluate the efficacy of Lupuzor over a period of subcutaneous injection of either Lupuzor 200 µg once a month, Lupuzor 200 µg twice a month or placebo.
The primary end point was defined as a decrease of at least four points in the SLEDAI score – an assessment of the clinical activity of lupus patients, where a lower score reflects lower disease activity.
It was found that 53 and 45% of patients were SLEDAI score responders in the Lupuzor once-a-month and twice-a-month groups, respectively, in comparison to 38% in the placebo group. In the moderate-to-severe subgroup, 62 and 48% of patients were responders in the Lupuzor once-a-month and twice-a-month groups, respectively, in contrast to 41% in the placebo group. Lupuzor was well tolerated and its safety profile was better than placebo.
Lupuzor is now licensed to Cephalon Inc., PLC, UK, and is in preparation for Phase III clinical trials. Frank Baldino Jr, Cephalon‘s Chairman and CEO stated: “We are pleased to have the opportunity to further develop Lupuzor and potentially bring a new medication to the lupus patients who have waited 50 years for new therapy.”
Source: ImmuPharma PLC, UK: www.immupharma.com