Alison Clayton | PubMed Health

PubMed2006

CD8 T-cell recognition of human 5T4 oncofetal antigen.

The 5T4 oncofetal antigen is expressed by a wide variety of human carcinomas, including colorectal, ovarian and gastric carcinomas. The restricted expression of 5T4 on tumor tissues as well as its implication in tumor progression and bad prognosis makes 5T4 a promising new candidate for immunotherapy. An MVA vaccine encoding 5T4 antigen has been successfully evaluated in preclinical studies in a murine tumor model. Here, we report the generation of human CD8 T cells specific for the 5T4 antigen by stimulation with autologous monocyte derived DC infected with a replication defective adenovirus encoding the 5T4 cDNA (Ad5T4). Analysis of several donors confirms a repertoire of such CD8 responses. In a parallel approach, incorporating the results of proteasome-mediated digestion of 5T4 derived 35-mer peptides and the potential high affinity epitopes predicted by a computer-based algorithm, we identified 8 putative HLA-A*0201-presented CD8 MHC class I epitopes of 5T4 antigen. Two of these generated specific CD8 T cells after restimulation with peptide loaded autologous DC and assay by cytotoxicity and IFN gamma ELISPOT. Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201 as judged by IFN gamma ELISPOT or ELISA. Also, HLA-A*0201 CD8 T cells recognized these peptides in a DC-Ad5T4 polyclonal response. In conclusion, there is a repertoire of CD8 T cell recognition of 5T4 in normal human donors and some candidate HLA-A*0201 epitopes have been identified.

Adenoviridae↗

PubMed2004

The changing face of HIV-associated lymphoma: what can we learn about optimal therapy inl the post highly active antiretroviral therapy era?

Epidemiological data indicate that the risk of developing non-Hodgkin lymphoma (NHL) in HIV positive individuals is related to age and CD4 count (i.e. degree of immunosuppression). The prognosis of patients with HIV-NHL has been shown to be linked to several features including age, stage, modified IPI, prior AIDS diagnosis, CD4 count, immunoblastic pathology, LDH, and HAART use. These features are, as would be expected, a mixture of prognostic factors relating to both the HIV, and to the NHL. Population studies indicate that the incidence of associated (HIV-NHL) may be reducing with the advent of HAART, although not all studies concur. However, most population-based studies have not as yet shown a significant improvement in the survival of patients with HIV-NHL with HAART. The optimal chemotherapy for these patients is unknown, although it is generally accepted that CNS prophylaxis is mandatory. There is currently no good evidence of any survival benefit with increased dose intensity from large RCT. However, it must be borne in mind that the large randomised studies comparing differing dose intensities were undertaken before the advent of effective HAART. There is some evidence that there may be a subset of good prognosis patients who may benefit from more intensive therapy. Given that the prognosis of patients with HIV can now be considerably improved with HAART, we cannot necessarily assume that the same results would apply with regard to chemotherapy dose intensity. There is some evidence that there is a survival benefit from the addition of HAART to chemotherapy, although this is retrospective. It is likely, however, that the reason for this is that the HAART improves the prognosis of the patients from their HIV, and therefore reduces the number of patients dying from other HIV-related illnesses whilst in remission from their lymphoma, as was seen in large numbers of patients in the earlier chemotherapy trials. It must not be forgotten that the prognosis of the patient's NHL is intimately linked to their prognosis with respect to the HIV. Although the number of patients with HIV-NHL is currently few, there is a need for more trials of chemotherapy, particularly now in the HAART era, when the prognosis from the point of view of the HIV has improved so much. In particular, the issue of dose intensity needs revisiting for patients whose overall prognosis can be improved by commencing HAART. Patients with HIV-NHL should be managed at specialist centres, and where possible should be managed as part of RCT.

Anti-HIV Agents↗

PubMedDate not supplied

A model for integrating hepatitis C services into an HIV/AIDS program.

Service provision to persons with or at risk for hepatitis C (HCV) has become an important goal for local health departments across the nation. The shared routes of HIV and HCV, the high coinfection rate of HIV/HCV, and the lack of federal or state funding to support HCV programs are reasons for integrating hepatitis C screening and treatment services into existing HIV/AIDS programs. Such an integration of health services conserves resources. This article reviews the development and progress of a county public health department program's integration of HIV/AIDS and HCV services and provides recommendations for other HIV/AIDS programs that might be considering integration of HIV/AIDS and HCV services.

AIDS-Related Opportunistic Infections↗