Many Mediocre Cancer Therapies Become Much Better When More Targeted to Cancerous Tissues

One of the important areas of cancer research and development that appears to receive a great deal of attention and funding, but in practice seems slow to make it from the laboratory to the clinic, is the targeting of therapeutics to cancerous cells. Reductio ad absurdum, near any of dozens of existing chemotherapeutics would do the job of completely clearing tumors, with minimal to no side-effects, if one could only find a way to delivery tiny amounts of the therapeutic to every cancer cell while avoiding every healthy cell. The inability to target treatments this effectively is exactly why cancer remains such a problem. Killing cells is easy. Killing only the desired cells is hard.

Today's research materials provide an example of this principle. Tumors compromise the immune system, and many of the more recent cancer therapies involve delivery of signals to rouse otherwise suppressed immune cells to unfettered aggression. This is a double-edged sword: an aggressive immune system is capable not only of attacking the cancer, but also of causing a great deal of harm to the patient in the worse cases. Still, this balance of benefit and harm is largely a better one for patients than is the case for chemotherapy. Why not make this delivery of immune-modulating signals much more targeted, however? As it turns out, this greatly improves the therapy.

'Drug factory' implants eliminate ovarian, colorectal cancer in mice

The researchers used implantable "drug factories" the size of a pinhead to deliver continuous, high doses of interleukin-2, a natural compound that activates white blood cells to fight cancer. The drug-producing beads can be implanted with minimally invasive surgery. Each contains cells engineered to produce interleukin-2 that are encased in a protective shell.

Interleukin-2 is a cytokine, a protein the immune system uses to recognize and fight disease. It is an FDA-approved cancer treatment, but the drug factories provoke a stronger immune response than existing interleukin-2 treatment regimens because the beads deliver higher concentrations of the protein directly to tumors. "Once we determined the correct dose - how many factories we needed - we were able to eradicate tumors in 100% of animals with ovarian cancer and in seven of eight animals with colorectal cancer. If you gave the same concentration of the protein through an IV pump, it would be extremely toxic. With the drug factories, the concentration we see elsewhere in the body, away from the tumor site, is actually lower than what patients have to tolerate with IV treatments. The high concentration is only at the tumor site."

Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors

Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome these limitations, we developed a clinically translatable cytokine delivery platform composed of polymer-encapsulated human ARPE-19 (RPE) cells that produce natural cytokines.

Tumor-adjacent administration of these capsules demonstrated predictable dose modulation with spatial and temporal control and enabled peritoneal cancer immunotherapy without systemic toxicities. Interleukin-2 (IL2)-producing cytokine factory treatment eradicated peritoneal tumors in ovarian and colorectal mouse models. Furthermore, computational pharmacokinetic modeling predicts clinical translatability to humans. Notably, this platform elicited T cell responses in non-human primates, consistent with reported biomarkers of treatment efficacy without toxicity. Combined, our findings demonstrate the safety and efficacy of IL2 cytokine factories in preclinical animal models and provide rationale for future clinical testing in humans.


Off topic: My grandmother (b.1940) are dying of sepsis after diagnosed with cancer 1ya. There is a company wit a solution:

Posted by: ciclo at March 9th, 2022 4:46 PM

It might (soon) be possible to target cancers with a mutation in the RAS gene by targeting the large amount of ferrous iron that they produce:

""Cobimetinib is a classic example of an anticancer drug that we know works well on its target, but it hasn't achieved its clinical potential because the same target is important in the skin and other normal tissues," said co-senior author Adam Renslo.

The scientists were able to synthesize a new form of cobimetinib equipped with a molecular sensor for ferrous iron. This means the drug remains inactive until it comes across ferrous iron in the cancer cells, which switches it on and selectively activates its anti-cancer effects.

The team demonstrated the effectiveness of the new drug, dubbed TRX-cobimetinib, through experiments on mouse models of KRAS-driven cancers. This showed that it was just as effective as cobimetinib at shrinking tumors, but did so without the typical adverse effects. With lower levels of toxicity, the scientists could then bring other cancer drugs into the mix to ramp up the attack, enabling combination treatments that could prevent tumor growth with even greater effectiveness.

"By removing toxicity from the equation, you're talking not just about one new drug, but 10 new combinations that you can now think about exploring in the clinic," said Renslo. "That would be the home run for this approach.""

Posted by: jimofoz at March 10th, 2022 5:12 AM

Many years ago a student in my lab developed a therapy using a bubble containing a cancer drug along with gangrene. When it hit the tumor the gangrene would burst the bubble and release the drug into the tumor. 90% efficacy in mice. He won 1st prize at a major scientific invention contest in California. Unfortunately he could not get approved for trials by the FDA or anywhere else.

Posted by: Mark Kelman at March 13th, 2022 11:56 AM

This could probably be said of many non-cancer rejuvenation treatments that only work modestly as well.

Posted by: K at March 14th, 2022 5:22 PM
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