PB006 AptaMLN

Current chemotherapeutic strategies used to treat melanoma have resulted in discouraging outcomes. Targeted therapies offer viable alternatives to reduce the adverse effects and systemic toxicity associated with conventional chemotherapy, as well as a means to improve its efficiency. According to this approach, a cytostatic drug reaches cancer cells selectively, leaving healthy cells unaffected, thereby allowing for an equivalent or improved therapeutic effect, all achieved while using a reduced drug dosage. The PB006 (AptaMLN) project aims to develop a conjugate bearing a known cytostatic drug molecule linked to an aptamer carrier designed to specifically recognize melanoma cells. The resulting new form of this drug is intended for use in targeted therapy, improving the safety and efficacy of melanoma treatment – a disease whose prevalence doubles every ten years.

OBJECTIVES

The goal of the project is to develop a conjugate of a known cytostatic drug molecule linked to an aptamer carrier which specifically recognizes a molecular target on the surface of melanoma cells. The conjugate will be selectively transported into cells which express the target, boosting drug activity against melanoma cells.

DESCRIPTION

Melanoma is a skin cancer resulting from exposure to UV light and other DNA-damaging factors. Prevalence of melanoma is very high and increasing – the number of new patients doubles every 10 years. Basic treatment options include surgical excision of the lesion. In some cases, adjuvant treatment is also applied, primarily immunotherapy or radiotherapy, which is associated with severe adverse effects. However, to date, use of conventional chemotherapy to treat melanoma has not been associated with satisfactory results.

Aptamers are short single-stranded oligonucleotides that bind molecular targets with high affinity and specificity. Although aptamers recognize and bind targets with activities comparable to antibodies, they have a number of advantages, including shorter generation times, lower costs of manufacturing, very low batch-to-batch variability, higher modifiability and better thermal stability. Also, by comparison to antibodies, aptamers exhibit lower immunogenicity, highlighting the possibility to eliminate side effects resulting from non-specific immunomodulatory effects.

Development of a conjugate comprising an aptamer carrier linked to a known anticancer drug provides an opportunity to increase the effectiveness of chemotherapy in melanoma patients, while reducing adverse events. These effects will derive from properties of the aptamer carrier, which will specifically recognize and bind to melanoma cells, initiating drug uptake.

PURE BIOLOGICS’ ROLE

Pure Biologics’ role in the PB006 project is to leverage its proprietary PureApta platform in order to identify aptamers that bind to a specific molecular target expressed by melanoma cells.

PROJECT PROGRESS

Two experimental cell models have been developed, which are currently being used for aptamer selection campaigns.

PROJECT DATA SHEET

Title: Development of new melanoma therapy based on aptamer carrier
Program: Smart Growth Operational Programme 2014-2020
Value: 1 411 510 PLN (for the entire consortium: 2 354 428,75 PLN)
Contribution of European Funds: 1 129 208 PLN (the entire consortium: 2 072 126,75 PLN)
Start: 1st January 2020
End: 30^th June 2021
Consortium members: Sieć Badawcza Łukasiewicz – PORT Polski Ośrodek Rozwoju Technologii, Pure Biologics S.A.