Grafting primary human T lymphocytes with cancer-specific chimeric single chain and two chain TCR

Abstract

Primary human activated T lymphocytes were genetically grafted with chimeric T cell receptors (TCR). Three domain single chain (sc-) TCR as well as two chain (tc-) TCR gene constructs were derived from the melanoma-specific cytotoxic human T cell (CTL) clone 82/30, and linked to the CD3-signaling element. Chimeric TCR ␣ and ␤ receptor genes were structurally designed to prevent pairing with endogenous TCR ␣ and ␤ chains in order to prevent the generation of unpredictable immune specificities. After transduction of polyclonally activated human peripheral blood lymphocytes

Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc ‘spacer’ domain in the extracellular moiety of chimeric antigen receptors avoids ‘off-target’ activation and unintended initiation of an innate immune response

“…Retroviral transduction of T cells with recombinant receptors was elsewhere described in detail. 15,[19][20][21][22] Receptor expression was monitored by flow cytometry.…”

Adenovirus targeting to HLA-A1/MAGE-A1-positive tumor cells by fusing a single-chain T-cell receptor with minor capsid protein IX

“…17 The gene encoding scTCR A1M1 was subcloned from the retroviral vector pBullet.VaVbCb. 46 The scTCR A1M1 sequence of pBullet. VaVbCb was originally constructed from the Va, Vb and Cb sequences from an HLA-A1/MAGE-A1-specific CTL clone MZ2-82/30 of patient MZ2.…”

Engineering T cells for cancer therapy

“…The probability of this occurring is unknown and the potential danger has to be carefully assessed and balanced against the potential benefit of treating patients with advanced disease. However, more recent studies have focused up engineering the antigen-specific TCRs in order to prevent pairing with endogenous TCR genes (Willemsen et al, 2000).…”