Antitope to produce manufacturing cell lines for two potential HIV vaccines

By Zachary Brennan contact

- Last updated on GMT

Antitope to produce manufacturing cell lines for two HIV vaccines

Related tags: Cell lines, Immune system

Abenza subsidiary Antitope has extended its relationship and will provide manufacturing cell lines for two developing HIV vaccines from the French National Institute of Health and Medical Research (INSERM); the National Health Agency for Research on AIDS and Hepatitis (ANRS); and the Baylor Institute for Immunology Research (BIIR).

INSERM-ANRS and the BIIR have developed the vaccines to target HIV antigens to dendritic cells (DC) using monoclonal antibodies fused to HIV antigens. Extensive preclinical data has demonstrated the high immunogenicity of the candidate vaccines.

Antitope will produce cell lines for GMP manufacture of two anti-CD40-HIV fusion proteins that INSERM-ANRS and BIIR are developing as potential therapeutic and prophylactic vaccines to treat HIV. The cell lines will be produced using Antitope’s Composite CHO technology.

High-expressing stable cell lines are grown in suspension media to produce high yields of fusion proteins in a chemically defined, serum-free medium. Transfection of the cells is performed using our pANT vector system. This system comprises a small vector sequence allowing for highly efficient trasfection​,” Neil Butt, VP of business development at Antitope, told “High protein expression is vital to keep manufacturing costs down and the pANT vectors maximise recombinant protein expression through the use of a proprietary UTR (untranslated terminal repeat) to enhance protein production and a modified dhfr gene allowing for the rapid amplification of vector copy numbers in the cells through methotrexate selection​.”

The antibody component of the fusion proteins has previously been humanized by Antitope using its composite human antibody technology.

Clinical studies have shown that many humanized antibodies produced by traditional engineering technologies are immunogenic in a proportion of patients​,” Butt added. “These antibodies were humanised usingComposite Human Antibodies™ which generates fully humanized antibodies that minimizes immunogenicity in patients. Antibody humanization uses multiple sequence segments derived from variable (V) regions of unrelated human antibodies, unlike other technologies that typically use a single human V region framework as acceptors for complementarity determining regions (CDRs) from starting antibodies (typically rodent)​. Through careful selection of human sequence segments and the application of ​in silico tools, CD4+ T cell epitopes are avoided so the risk of immunogenicity is reduced compared to standard humanized antibodies whilst antibody affinity and specificity is maintained​.”

Phase I and Phase II clinical trials will be conducted in France to test the immunogenicity and efficacy of these DC-targeting vaccines developed by INSERM-ANRS in partnership with the BIIR.

Butt also told us that technology has been applied to multiple antibodies, though Gilead’s simtuzumab is the furthest advanced in the clinic.

Abzena's Chief Scientific Officer, Matthew Baker, added, “This project further extends our relationship with BIIR in developing a range of therapeutic vaccines for the treatment of diseases such as HIV​.”

The move also comes as Antitope has signed on to make the manufacturing cell line for BIIR’s head, neck and cervical cancer vaccine​.

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