For patients with B-cell cancers like acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) that don’t respond to or relapse after chemotherapy, prognosis remains poor, and nearly half of patients will lose the fight against their disease.1 However, the field of cancer care is progressing rapidly, and additional options beyond chemotherapy have been made available to patients.
Monoclonal antibodies, also known as mAbs, are less toxic and have an ability to selectively bind to a specific antigen on the surface of a cancer cell.2 However, once cancer cells evolve and find ways to resist treatment, tumors can evade destruction.3
Following allogeneic hematopoietic stem cell transplantation, a patient’s immune system can develop a response to fight back against cancer.4 This response includes cytotoxic T lymphocytes or CTLs which have enormous therapeutic potential to treat cancer.4
All things considered, a promising therapy for hematologic malignancies would redirect CTLs to fight back against tumors, maintaining the selectivity of mAbs, and preventing immune escape.2-4
That’s where Bispecific T cell Engager (BiTE®) immuno-oncology comes into play.
BiTE® technology refers to a type of fusion protein composed of two loosely-linked, single-chain antibodies. Each antibody has a distinct target, lending to the name of bispecific: one binds to a specific surface antigen on the cancer cell, while the other binds to a protein found on the surface of cytotoxic T cells.5
“A BiTE® is an off-the-shelf biologic molecule that’s designed to bridge the T cells in the immune system to a tumor-selective antigen,” says Dr. Gregory Friberg, vice president, global development at Amgen in Thousand Oaks, Calif. This bridge is designed to induce T cell activation, expansion, and ultimately, lysis or death of cancer cells.5
“It’s a molecule that serves as a linker to help the immune cells find a tumor they might not have otherwise,” says Dr. Friberg.
BiTE® technology has come a long way in almost 30 years of development, with many structural iterations.6 Dr. Friberg believes that Amgen, with a proof-of-concept molecule, is leading the way to improve upon BiTE® constructs, the company’s proprietary platform.
The combination of three key factors distinguishes BiTE® from other bispecific antibody constructs: high potency of tumor cell death, strict target cell-dependent T-cell activation, and serial tumor destruction even with lower numbers of T cells.5
Building on BiTE®’s success, Amgen is currently exploring the use of BiTE® for other cancers, Dr. Friberg explains. These include other hematologic malignancies such as multiple myeloma and acute myeloid leukemia and even solid tumors, such as non-small cell lung cancer.
“There’s no reason that one particular disease should be susceptible to this technology,” Dr. Friberg explains. “It really is more of a case of ‘can we redirect T-cells to target tumors expressing a given antigen.’ There will probably be a different profiles based for each individual target and product.”
According to Dr. Friberg, BiTE® technology is currently intended for complementary use with other approaches. “Physicians need multiple arrows in their quiver. It’s our vision in investigating this technology that this will be an important part of the treatment strategies, but not the only treatment,” he explains.
He elaborates, “Combinations not only with chemotherapies or antibody drug conjugates, but also with other immunotherapies like anti-PD1 antibodies may be studied. We’ll ultimately have to test those in clinic and see what the right combination is for each clinical scenario.”
So what’s next for BiTE®?
Second-generation BiTE®anitibodies, which could have a longer half-life than their first-generation predecessors, are being studied.7 The hope is that second-generation BiTE®antibodies may not need to be given as a continuous infusion, Dr. Friberg explains.
“That makes certain indications much more plausible to bring our product to market,” Dr. Friberg says.
Although other pharmaceutical companies are working to develop new oncologic therapies, Dr. Friberg believes that Amgen’s BiTE® platform could offer patients something unique.
“The concept of providing an off-the-shelf therapy may distinguish this from individualized cellular therapy,” he states.
Dr. Friberg concludes, “Ultimately, it’s going to be a question of trying each target, looking at specific therapeutic windows, and if they are approved by the FDA, deploying these agents not only for patients who need more therapy, but in those that we think this mechanism of action offers the greatest potential.”
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