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Volume 3
Journal of Neurology and Clinical Neuroscience
Neurology 2019 | Neuropsychology 2019 | Drug Delivery Summit 2019
June 24-25, 2019
June 24-25, 2019 | Rome, Italy
Neurology and Healthcare
3
rd
WorldDrug Delivery and Formulations Summit
Clinical and Experimental Neuropsychology
4
th
International Conference on
International Conference on
&
Enhanced tumor toxicity and reduced off-target toxicity by pretargeting mammary carcinoma with
bispecific antibody complexes and dual polymer-pro- drug conjugates
Ban An Khaw, Na Yoon Kim
and
Prashant Bhattarai
Northeastern University, USA
Statement of the Problem:
Conventional chemotherapy is associate with severe off target toxicities. Pretargeting of
high specific activity Polymer-Pro-Drug Conjugates (PPDCs) should reduce off-target toxicity and increase therapeutic
efficacy. We now report enhanced therapeutic efficacy in a murine mammary carcinoma model pretargeted with
Bispecific Botinylated anti-DTPAAntibody Complexes (BSAbC) and targeting with single or double PPDCs containing
Doxorubicin (Dox) or Paclitaxel (Ptxl). No hematological- nor cardio-toxicity were seen in animals treated with PPDCs.
Methods:
Biotin-anti-DTPA antibody BSAbC was used to pretarget murine mammary carcinoma 4T1, that over-express
biotin receptors grown in Balb/C mice. Experiment treatments were as follows: placebo, Dox, Ptxl, pretargeting with
BSAbC followed by DOX-PPDCs, Ptxl-PPDCs, or combination of both PPDCs injected weekly. Tumor volumes were
measured daily. Then, tumors were harvested, weighed and TUNEL staining was performed to assess apoptosis. Blood
samples were obtained for H &E staining to determine hematological toxicities. Hearts from experimental animals were
analyzed by fluorescence microscopy for Dox cardiotoxicity.
Results:
Maximal tumor growth suppression was observed in the combination PPDC treatment group (67mg). Individual
DOX-PPDCs or Ptxl-PPDCs treatment were better than Dox or Ptxl treated tumors. The placebo group tumor size was 670
mg. The extent of apoptosis by TUNEL staining was inversely proportional to with tumor size. Fluorescence microscopy
showed that Dox treatment had Dox fluorescence in the myocardium whereas hearts from pretargeted PPDC groups
showed no Dox accumulation. There was no hematological toxicity in single PPDC or dual PPDC therapy groups whereas
Dox and Ptxl treatment groups showed toxicities (p<0.05-0.01 respectively).
Conclusion:
Biotin receptor expressing murine 4T1 carcinoma could be pretargeted and targeted with single or dual
PPDCs to obtain optimal tumor regression. Both cardiotoxicity and hematological toxicities were not observed following
treatment with PPDCs. This therapeutic approach could provide highly effective cancer therapywith no off-targeted toxicity.
J Neurol Clin Neurosci, Volume 3