Contacts
  • Increase
  • Decrease
  • Normal
Accessibility

TK

The best treatment currently available for leukaemias and other haematological malignancies is the transplant of haematopoietic stem cells (HSCT) from healthy donors. However, fully compatible donors are available only for approximately 50% of patients.
TK is an ex vivo cell therapy, enabling safe HSCT from partially compatible haplo-identical donors (e.g. mother, father, brothers or sisters), who are available for nearly all patients.

Without the add-back of TK therapy, the successful outcome of partially compatible transplants is hampered by delay of patient’s immune-reconstitution, which is needed to prevent opportunistic infections, or by development of Graft versus Host Disease (GvHD), a systemic immune reaction mediated by donor T cells against the patient’s organs and tissues.

TK is based on the genetic engineering of T cells from the HSC donor to express a gene (HSV-TK) which makes these cells sensitive to the antiviral drug Ganciclovir. Treatment with Ganciclovir at GvHD onset kills the donor T cells involved in the reaction, thus abrogating GvHD.

Administration of TK therapy following HSCT promotes early and sustained reconstitution of the immune system, thereby reducing transplant-related mortality. Moreover, it allows preservation of the anti-tumour activity of the graft, thus preventing disease relapse and improving the quality of life.

A randomised Phase III trial is currently in progress on adult high-risk leukaemia  patients  undergoing haplo-transplant.

FIG. 1 Immunodeficient NOD/Scid mice received a transplant of human skin, prior to the intravenous infusion of human TK+ or untransduced lymphocytes. Few days after injection, mice were treated with ganciclovir (+) or left untreated (-).
At day 7 of treatment, the transplanted skin was harvested and analyzed for the presence of infiltrating  human lymphocytes by histopathology after staining with hematoxylin and eosin (10x top row, 40x middle row) or with monoclonal anti-human-CD3 antibodies (40x bottom row).
Treatment with ganciclovir eliminates the TK-expressing human lymphocytes that are causing a Graft versus Host reaction.

 

MolMed S.p.A. Via Olgettina, 58 - 20132 Milano, Italy | Phone +39 0221277.1 - Fax +39 02 21277.325 | info@molmed.com - www.molmed.com
Share capital € 11,019,314.98 fully paid - Office of Milan Company Registry number 1506630 - Tax identification number 11887610159