Tag: CAR-T

  • CAR-T Bests Solid Tumors

    The promise of immune cell therapies is to direct the incredible sophistication of the immune system to the medical targets we want to hit. In the case of CAR-T cells, we take a patient’s own immune T-cells and “program” them through genetic modification to go after cancer cells. While the process of the genetic modification to create those cells is still incredibly expensive and challenging, we’ve seen amazing progress with CAR-T in liquid tumors (e.g., leukemias, lymphomas, etc).

    But, when it comes to solid tumors, it’s been far more challenging. Enter this Phase II clinical trial from China (summarized in Nature News). The researchers performed a random controlled trial on 266 patients with gastric or gastro-esophageal cancer who resisted previous treatment and assigned 2/3 to receive CAR-T or best-medical-care (the control) otherwise. The results (see the survival curve below) are impressive — while the median progression-free survival is only about 1.5 months different, it’s very clear that by month 8 there are no progression-free patients in the control group but something like ~25% of the CAR-T group.

    The side effect profile is still challenging (with 99% of patients in CAR-T group experiencing moderately severe side effects) but this is (sadly) to be expected with CAR-T treatments.

    While it remains to be seen how this scales up in a Phase III study with a larger population, this is incredibly promising finding — giving clinicians a new tool in their arsenal for dealing with a wider range of cancer targets as well as suggesting that cell therapies still have more tricks up their sleeves


  • Iovance brings cell therapy to solid tumors

    Immune cell therapy — the use of modified immune cells directly to control cancer and autoimmune disease — has shown incredible results in liquid tumors (cancers of the blood and bone marrow like lymphoma, leukemia, etc), but has stumbled in addressing solid tumors.

    Iovance, which recently had its drug lifileucel approved by the FDA to treat advanced melanoma, has demonstrated an interesting spin on the cellular path which may prove to be effective in solid tumors. They extract Tumor-Infiltrating Lymphocytes (TILs), immune cells that are already “trying” to attack a solid tumor directly. Iovance then treats those TILs with their own proprietary process to expand the number of those cells and “further activate” them (to resist a tumor’s efforts to inactivate immune cells that may come after them) before reintroducing them to the patient.

    This is logistically very challenging (not dissimilar to what patients awaiting other cell therapies or Vertex’s new sickle cell treatment need to go through) as it also requires chemotherapy for lymphocyte depletion in the patient prior to reintroduction of the activated TILs. But, the upshot is that you now have an expanded population of cells known to be predisposed to attacking a solid tumor that can now resist the tumor’s immune suppression efforts.

    And, they’ve presented some impressive 4-year followup data on a study of advanced melanoma in patients who have already failed immune checkpoint inhibitor therapy, enough to convince the FDA of their effectiveness!

    To me, the beauty of this method is that it can work across tumor types. Iovance’s process (from what I’ve gleamed from their posters & presentations) works by getting more and more activated immune cells. Because they’re derived from the patient, these cells are already predisposed to attack the particular molecular targets of their tumor.

    This is contrast to most other immune cell therapy approaches (like CAR-T) where the process is inherently target-specific (i.e. get cells that go after this particular marker on this particular tumor) and each new target / tumor requires R&D work to validate. Couple this with the fact that TILs are already the body’s first line of defense against solid tumors and you may have an interesting platform for immune cell therapy in solid tumors.

    The devil’s in the details and requires more clinical study on more cancer types, but suffice to say, I think this is incredibly exciting!


  • Complex operations for gene editing therapies

    Gene editing makes possible new therapies and actual cures (not just treatments) that were previously not. But, one thing that doesn’t get discussed a great deal is how these new gene editing-based therapies throw the “take two and call me in the morning” model out the window.

    This interesting piece in BioPharmaDive gives a fascinating look at all the steps for a gene editing therapy for sickle cell disease that Vertex Pharmaceuticals is awaiting FDA approval for. The steps include:

    • referral by hematologist (not to mention insurance approval!)
    • collection of cells (probably via bone marrow extraction)
    • (partial) myeloablation of the patient
    • shipping the cells to a manufacturing facility
    • manufacturing facility applies gene editing on the cells
    • shipping of cells back
    • infusion of the gene edited cells to the patient (so they hopefully engraft back in their bone marrow)

    Each step is complicated and has their own set of risks. And, while there are many economic aspects of this that are similar to more traditional drug regimens (high price points, deep biological understanding of disease, complicated manufacturing [esp for biologicals], medical / insurance outreach, patient education, etc.), gene editing-based therapies (which can also include CAR-T therapy) now require a level of ongoing operational complexity that the biotech/pharmaceutical industries will need to adapt to if we want to bring these therapies to more people.