Background
and Objective: Harnessing immune system and its powerful
arm, T lymphocytes, against tumor cells are yielding promising results in
cancer immunotherapy. Using two arms of immune system in the designing of
engineered T cells expressing chimeric receptors with anti-HER2 nanobody (camelid
single domain antibody) seems to be an effective strategy in the targeted
cancer therapy.   Materials
and Methods: HER2 specific nanobodies were used as a
recognition site for constructing chimeric receptors
NbHER2-HHIgG3-CD28-OX40-CD3ζ (elongated) and NbHER2-HIgG3-CD28-OX40-CD3ζ
(short) on the membrane of T cells. Expression of chimeric receptors was
evaluated by RT-PCR. Function of engineered T cells against cancer cells was
assessed by the secretion of interleukin 2 and LDH cytotoxicity assay.   Results:
Elongated
chimeric receptors with nanobodies RR6 and RR16 that target juxtamembranal
domain of HER2 antigen functioned better than elongated constructs containing
nanobodies RR4 and RR10. In contrast, nanobodies RR4 and RR10 used in the short
chimeric receptors showed substantial results.   Conclusion:
Based on binding properties of nanobody, functional chimeric receptors can be designed and
engineered T lymphocytes containing the mentioned receptors can be generated
that substantially recognize and kill breast cancer cells.