Over the past several months, it’s been impossible to ignore the wave of investment and enthusiasm surrounding so-called ‘in vivo CAR-T’ approaches. At least half a dozen major deals have been announced in this space, signaling a surge of excitement. Some might expect this to worry us at Alloplex—but instead, I’m increasingly confident that we are pursuing a distinctly different, and ultimately more promising, corner of the cellular therapy landscape.

This “in vivo CAR-T” movement rests on a fundamental misclassification that seems driven more by marketing than science: *in vivo CAR-T is not cell therapy—it is gene therapy*. The approach relies on administering lipid nanoparticles (LNPs) carrying mRNA that encodes gene-editing enzymes directly into patients.

That distinction matters, particularly for safety. Unlike ex vivo cell therapy, there are no quality control measures ensuring which cells take up the nanoparticles or how accurately the gene edits occur. The larger question is whether regulators—and patients—will accept the systemic delivery of uncontrolled gene-editing enzymes that could induce permanent, unpredictable genetic changes.

A recent example underscores this concern: Intellia Therapeutics halted two trials after observing liver toxicity linked to its LNP-based delivery system. This illustrates that even before considering off-target edits, the nanoparticles themselves can be inherently toxic. While the risks might be justified in rare diseases with few alternatives, they become far harder to rationalize when targeting large cancer populations.

Gene Therapy V Cellular 

The in vivo CAR-T concept depends on introducing gene-editing enzymes into the bloodstream, hoping they act only on intended cells. But gene-editing tools can only make small, discrete genetic modifications—such as inserting a CAR gene.

By contrast, Alloplex’s immune cell training platform drives complex, multi-dimensional cellular reprogramming that simply cannot be achieved by a single vector making a single edit, no matter how advanced. Our cell training process depends on precise combinations of reagents—like cytokines—under tightly controlled laboratory conditions that cannot be replicated, much less tolerated in vivo.

In short: gene therapy modifies; immune cell training evolves.

Even if in vivo CAR-T approaches ultimately succeed, they are far more likely to disrupt the first-generation CAR-T companies which are reliant on single-step gene edits, than to compete with Alloplex’s fundamentally different strategy.

Debunking the ‘off-the-shelf’ myth

Much of the excitement around in vivo CAR-T is tied to another pervasive industry myth—that the future of cell therapy must be “off-the-shelf” or allogeneic. It’s time to challenge that assumption.

The notion that personalized cell therapy is “too hard” or “too inconvenient” has already led to billions being spent chasing a one-size-fits-all dream that doesn’t align with the biological reality of human diversity.

We accept individualized treatment planning in nearly every serious medical intervention—surgeries, cancer protocols, transplants—yet somehow insist that cellular therapy must be mass-produced like pills. That’s not innovation; that’s dogma.

Personalized cellular therapies like SUPLEXA are inherently tailored to each patient, delivering high-quality, individualized care that can also be economically viable. While it’s too early in SUPLEXA’s development to discuss detailed pharmaco-economics and price, there is no intrinsic reason why manufacturing must be expensive, especially since SUPLEXA manufacturing does not utilize expensive gene editing vectors. 

*With regional production, streamlined logistics, and industrialized cell-processing efficiencies, SUPLEXA could be delivered at scale at costs comparable to current antibody therapies.*

The goal is not to industrialize for its own sake, but to understand that that industrialization is available for improving any therapy that works — and that remains Alloplex’s unwavering focus.

The Alloplex advantage: safety and complexity

What makes our work especially exciting is that the highly active cells generated through immune cell training process have already demonstrated a remarkably favorable safety profile, with no clinical side effects observed to date. This wide therapeutic window allows us to explore increasingly complex combinations without amplifying toxicities — an exceedingly favorable but rare situation in drug development.

It is not often one can work with such a potent biological platform that also offers such inherent safety.

A call for deeper thinking

My hope is that the people, institutions, and nations guiding major biotech investments take a moment to look behind the curtain—to question the assumptions and marketing narratives that risk sidelining some of the most promising scientific breakthroughs before they’ve been fully evaluated.

At Alloplex Biotherapeutics, our success—and our impact on patients worldwide—will depend on one thing above all: delivering a product that truly works and makes people better. While others may chase valuations and buzzwords, we’ll continue to stay grounded in data, driven by science, and guided by results. There really is no other path to enduring success.