Current State of Antibody Drug Conjugates: A Look into the Future with DNA Origami Nanobots

Current State of Antibody Drug Conjugates: A Look into the Future with DNA Origami Nanobots

Antibody Drug Conjugates (ADCs) have emerged as a beacon of hope in the fight against cancer. These complex molecules ingeniously harness the targeting capabilities of antibodies with the killing power of cytotoxic drugs. The aim? Precise delivery of therapeutic agents to the cancerous cells while sparing healthy ones. But like every revolutionary approach, ADCs are not without their challenges. The future, however, holds exciting potential, particularly with the advancements made by DNA Nanobots and other DNA origami specialists.

The ADC Landscape Today

ADCs consist of three main components: the monoclonal antibody, a linker, and a cytotoxic drug. The antibody ensures specificity by binding to antigens predominantly expressed on tumor cells. Once internalized, the drug is released to execute its lethal effect. Over the last decade, several ADCs have been approved for clinical use, and many more are undergoing trials, illustrating the increasing confidence in this therapeutic strategy.  Currently (as of 2023), there are 13 FDA approved ADCs for treatment of a variety of cancers with over 100 new ADCs in clinical trials.

Challenges in ADCs

However, ADCs face numerous challenges in their development. They must demonstrate stability in the bloodstream, ensure efficient drug release upon target binding, and avoid off-target toxicity. There’s also the issue of drug resistance and heterogeneity among tumor cells, which can undermine efficacy.

1. Identifying New Targets: Identifying cancer-specific targets while sparing healthy cells is challenging. Tumors often share molecular markers with normal cells, making distinct targets elusive. Additionally, tumor heterogeneity and evolutionary pressures can alter these markers, complicating precise targeting. Finding consistent, exclusive cancer markers remains a significant hurdle.
2. Conjugating Without Changing Effect: New payload crosslinking offers enhanced drug stability and release control, but achieving consistent linkages without affecting drug potency or target specificity presents challenges in ADC development.
3. Limited Drug Payload: Traditional ADCs have a limited drug-to-antibody ratio (DAR), restricting the number of drug molecules per antibody. This limitation can impact the therapeutic potency and range of applications for these ADCs in complex clinical scenarios.

Promising Horizon with DNA Origami Nanobots

DNA origami, the art of folding DNA to create intricate nanostructures, is an evolving field. DNA origami nanobots have the potential to revolutionize the ADC landscape. How? Let’s delve into some of the ways:

1. Enhanced Specificity and Reduced Toxicity: With their customizable structures, DNA origami nanobots can be designed to recognize multiple tumor markers. This means they can enhance the precision of drug delivery, potentially reducing the harm to healthy cells.
2. Increased Payload: DNA nanobots can carry multiple drug molecules, increasing the payload and potentially boosting therapeutic efficacy. Increasing the DAR to 100+, this might even allow for combination therapies within a single nanobot.
3. Customizable Release Mechanisms: DNA nanobots can be designed with condition-responsive linkers. This ensures that the drug is released only under specific conditions, such as the acidic environment of a tumor cell.
4. Bypassing Drug Resistance: By delivering a cocktail of drugs or by targeting multiple markers, DNA nanobots can potentially counteract drug resistance, a frequent challenge in cancer therapy.

Collaborative Future: ADCs and DNA Origami Nanobots

While DNA origami holds great promise, it doesn’t mean the conventional ADC design will become obsolete. Instead, the future might see a collaborative approach. ADCs could be enhanced using DNA origami techniques, inheriting the benefits of both worlds.  Expanding the capabilities

Conclusion

Antibody Drug Conjugates are undoubtedly a milestone in targeted cancer therapy. But as with any frontier, there are challenges to overcome. The DNA origami nanobot technology, with its precision and programmability, is poised to usher in a new era of ADCs, making them even more efficient, specific, and versatile.

The future is on the horizon, and it seems set to merge the biological genius of ADCs with the engineering prowess of DNA Nanobots.

At DNA Nanobots we are experts in a field that is about to explode. If you have a therapeutic that you want delivered, we would love to help you do that.  You provide the therapeutic, we provide the vehicle.  Contact us at info@dnananobots.com or click below anytime.

by Patrick Halley, Co-Founder and CTO