Minibioreactor of co-cultured human immune cells allows immunofunction and immunotoxicity evaluation.

AFFiRiS is to evaluate ProBioGen’s Human Artificial Lymph Node (HuALN) technology as a tool to investigate the effects of its peptide vaccine candidates on the human immune system. AFFiRiS says that it expects the technology will help in the selection of the most appropriate vaccine candidates and speed the progression of its pipeline into clinical trials.

“We have been looking for a system like the HuALN for quite a long time and are excited by the possibilities the system offers to test our peptide vaccine candidates,” remarks Walter Schmidt, Ph.D., AFFiRiS CEO.

ProBioGen has developed the HuALN platform as a human cell-based in vitro system to help evaluate the immunofunction and immunotoxicity of drug candidates. The aim is to bridge the gap between preclinical and clinical trials.

The HuALN system comprises human T cells, B cells, and dendritic cells from selected donors, cultivated in the 3-D matrix of a miniaturized bioreactor. ProBioGen claims that within this matrix the cells self-organize into immunocompetent micro-organoid structures. The co-culture system can be perfused and maintained over long periods of time, allowing repeated exposure of the cells to test substances.

Read-outs from the test system include soluble and cellular biomarkers including induced cytokine secretion profiles to characterize T cell mediated immune responses, the firm points out. The cells can also be harvested after bioreactor operation for functional testing and analysis of surface biomarkers. 

AFFiRiS is developing synthetic peptide vaccines against chronic diseases including Alzheimer disease, Parkinson disease, and atherosclerosis. Designed as short peptides that function as B-cell epitopes, the vaccines are expected to induce antibody-mediated immune responses.

The vaccine technology hinges on AFFiRiS’ Affitome technology, which uses a molecular mimicry approach to develop an antigenic peptide that is unrelated in sequence to the native antigen. The firm says this technique has a number of advantages in comparison with traditional vaccination technologies. These include the immunologically foreign nature of the candidate peptide sequence, which negates the problems associated with triggering immune responses to nonimmunogenic self-antigens. Conversely, the ability to fine-tune the peptide sequences means it is possible to design vaccine candidates that will not cross-react with native, healthy proteins, according to AFFiRis.

The firm’s lead vaccine candidate, AD02, targets beta amyloid for the treatment of Alzheimer disease and is currently undergoing Phase II trials. A second Alzheimer candidate is in Phase I. A Parkinson’s disease candidate, PD01, is expected to enter clinical development during early 2011.

GlaxoSmithKline negotiated a licence to AFFiRis’ Alzheimer disease vaccine program in 2008. Under the terms of the deal, AFFiRiS received a €22.5 million (about $27.47 million) up-front payment and could earn a total of some €430 million (almost $525 million) in development and commercial milestones.

GSK has exclusive rights to develop and commercialize two candidates based on the AFFiTOPE technology. In addition, it has an exclusive option to develop and commercialize alternative Alzheimer disease vaccine candidates.

ProBioGen specializes in mammalian cell engineering and cell culture. Products and services in addition to the HuALN technology include proprietary and customized designer cell lines for protein and vaccine production, fast-track screening of high-producer cell lines, and what the firm describes as a new generation of disposable bioreactors. At the end of April the firm reported on a contract with Virdante Biopharmaceuticals, through which it will contribute producer cell-line development and process engineering for one of Virdante’s therapeutic proteins.

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