Localized Delivery Minimizes Side Effects of Immunotherapy

The American Cancer Society reports that over 600,000 Americans lost their lives to cancer in the previous year. Medical progress has been shaped by the unwavering quest to understand this complex disease, leading to the development of less invasive yet highly effective treatment procedures.

Localized Delivery Minimizes Side Effects of Immunotherapy

(Standing, from left) Rong Tong, Associate Professor in Chemical Engineering; Wenjun “Rebecca” Cai, Associate Professor in Materials Science and Engineering; Eungyo Jang; and Ziyu Huo gather around Liqian Niu (seated), who is working with a Luminex 200 machine used to analyze tumor cytokine levels. Image Credit: Hailey Wade for Virginia Tech.

The use of immunotherapy as a potential remedy is growing. Using immunotherapy, one can use the body's immune system to combat cancerous cells. A method has been discovered by College of Engineering researchers to transform a treatment procedure into an innovative practice. 

Together with Wenjun “Rebecca” Cai, an Associate Professor of Materials Science and Engineering, and Rong Tong, an Associate Professor of Chemical Engineering, we are investigating a cancer immunotherapy treatment that has long piqued researchers' interest. 

Tong and Cai described their strategy in detail in a recently published paper in the journal Science Advances. It entails reprogramming the body's immune cells to target and eliminate cancer cells. The protein cytokine is widely used in this therapeutic approach. 

The body's immune cells release cytokines, which are tiny protein molecules that function as intercellular biochemical messengers and help synchronize the immune response. 

Cytokines are potent and highly effective at stimulating the immune cells to eliminate cancer cells, the problem is they are so potent that if they roam freely throughout the body, they will activate every immune cell they encounter, which can cause an overactive immune response and potentially fatal side effects.”

Rong Tong, Associate Professor, Chemical Engineering, Virginia Polytechnic Institute

Tong and Cai have devised a novel method for using cytokine proteins as a possible immunotherapy treatment in conjunction with graduate students in chemical engineering, materials science, and engineering. 

In contrast to earlier ones, their approach guarantees that the immune cell-stimulating cytokines efficiently localize within the tumors for weeks while maintaining the cytokine's reactivity and structural integrity. 

Combining Forces to Take Down Cancer Cells 

Current cancer treatments, like chemotherapy, lack the ability to differentiate between healthy cells and cancerous ones. Chemotherapy attacks all of the body's cells when a patient has cancer, which can result in adverse effects like weariness and hair loss. 

One promising substitute for traditional cancer treatment is to activate the body's immune system to target tumors. Cytokines can be delivered to the tumor to stimulate immune cells, but overstimulating healthy cells can have detrimental side effects. 

Scientists determined a while ago that cytokines can be used to activate and fight against tumors, but they did not know how to localize them inside the tumor while not exposing toxicity to the rest of the body, chemical engineers can look at this from an engineering approach and use their knowledge to help refine and elevate the effectiveness of the cytokines so they can work inside the body effectively.”

Rong Tong, Associate Professor, Chemical Engineering, Virginia Polytechnic Institute 

The research team's objective is to strike a balance between eliminating cancer cells from the body and protecting healthy cells.

 Tong and his pupils used their knowledge to develop unique particles with distinguishable sizes that aid in locating the drug's destination ito achieve this aim. Once injected into the body, these microparticles are intended to remain within the tumor environment. Cai and her pupils measured the surface characteristics of these particles. 

In the field of materials science and engineering, we study the surface chemistry and mechanical behavior of materials, such as the specialized particle created for this project, surface engineering and characterization, along with particle size, play important roles in controlled drug delivery, ensuring prolonged drug presence and sustained therapeutic effectiveness.”

Wenjun “Rebecca” Cai, Associate Professor, Materials Science and Engineering, Virginia Polytechnic Institute 

Tong and his students in chemical engineering came up with a creative way to guarantee effective drug delivery that: 

  • Limits the damage that cytokines can do to healthy cells by attaching themselves to these novel microparticles.
  • Permits the recently attached cytokines to activate immune systems and enlist the help of immune cells to combat cancer cells. 

Tong said, “Our strategy not only minimizes cytokine-induced harm to healthy cells but also prolongs cytokine retention within the tumor, this helps facilitate the recruitment of immune cells for targeted tumor attack.” 

The subsequent phase of the procedure entails combining the novel, targeted cytokine therapy approach with commercially accessible, FDA-approved checkpoint blockade antibodies. This reconstitutes the previously silenced tumor immune cells, enabling them to combat the cancerous cells. 

Tong explained, “When there is a tumor inside the body, the body’s immune cells are being deactivated by the cancer cells, the FDA-approved checkpoint blocking antibody helps “take off the brakes” that tumors put on immune cells, while the cytokine molecules “step on the gas” to jump-start the immune system and get an immune cell army to fight cancer cells. These two approaches work together to activate immune cells.” 

In their study, the combination of the particle-anchored cytokine and checkpoint antibodies proved effective in eliminating a large number of tumors. 

Engineering an Impact on Cancer Treatment

The members of the team hope that their influence on immunotherapy treatment is a part of a larger trend toward cancer treatment methods that do not harm healthy cells. The team believes that other kinds of immunostimulatory medications may be delivered in the future using the novel strategy of affixing cytokines to particles.

 Tong said, “Researchers are still looking for safer and more effective cancer treatments, this motivation is what drives us to develop new technologies in the field. The whole class of drugs that are employed to jump-start the immune system to fight cancer cells has largely not yet succeeded. Our goal is to create novel solutions that allow researchers to test these drugs with existing FDA-approved therapeutics, ensuring both safety and enhanced efficacy.”

 According to Cai, the nature of cancer treatment research necessitates knowledge from several engineering specialties.

 Cai said, “I view this project as a perfect marriage between chemical engineering and materials science, the former focuses on the synthesis and drug delivery part, the latter on applying advanced materials characterization. This collaboration not only accelerates immunotherapy research but also has the ability to transform cancer treatment.”

Source:
Journal reference:

Niu, L., et al. (2024) Noncovalently particle-anchored cytokines with prolonged tumor retention safely elicit potent antitumor immunity. Science Advances. doi.org/10.1126/sciadv.adk7695

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