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by Dr. C.H. Weaver M.D. updated 4/2022

The BiTE® antibody construct represents an innovative immunotherapy approach that helps the body’s immune system target cancer cells and appears very promising for the treatment of advanced lymphomas and multiple myeloma.

BiTE is short for "bispecific T cell engager". BiTEs are antibodies with two arms. One arm of the drug attaches to a specific protein on the tumor cell. The other arm of the BiTE activates immune cells in the patient to kill the cancer cells.

CancerConnect Community490 General

CAR-T cell immunotherapy is the most recent major innovation in treating advanced lymphoma, having been shown superior to stem cell transplantation. Now its BiTE, and a big question is whether BiTE could ultimately be more broadly beneficial that CAR-T?

There are several differences between BiTE and CAR-T cells and a key one is that BiTEs has the advantage of being “off the shelf” meaning the same product can be given to all patients. CAR-T's must be made from cells taken from each patient and hence is more time consuming and potentially more expensive.

Individuals with advanced-refractory Hodgkin and non-Hodgkin lymphoma should consider being evaluated at cancer centers offering CAR-T and BiTE therapies as they are likely to produce better outcomes than more standard treatment approaches. 

Blincyto (blinatumomab) in ALL

Blincyto was the first BiTE® antibody constructs developed and was approved for the treatment of Acute Lymphoblastic Leukemia in 2015. The BiTE® antibody construct is designed to direct the body’s cell-destroying T cells against target cells expressing CD19, a protein found on the surface of B-cell derived leukemias and lymphomas. Blincyto as been demonstrated to prolong survival in acute lymphoblastic leukemia and doctors are working to determine the best may to incorporate it into the overall treatment strategy. Learn more about Blincyto in ALL.

Blincyto has also been shown to be safe and capable of inducing long term remissions in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).1

Doctors reported a follow-up analysis of the initial 38 patients with B cell NHL who participated in the MT103-104 study, and found no evidence of long-term side effects with Blincyto as the effective dose. The median overall survival for individuals with relapsed/refractory NHL was 4.6 years and patients who achieved a response had an average survival of 7.7 years.

REGN 1979

In a Phase 1 proof-of-concept trial, the experimental REGN1979 bi-specific antibody demonstrated a 100% overall and 80% complete response rate in 10 patients with relapsed or refractory follicular lymphoma. REGN1979 is a bi-specific monoclonal antibody designed to trigger the killing of cancer cells by binding to both CD3 on immune system T-cells and CD20 on B-cell lymphomas.

During a conference call in May 2019 Regeneron's Chief Scientific Officer George Yancopoulos briefly mentioned that there were two fatalities in the RGN1979 program in a small 30 patient trial combining RGN1979 with the company’s PD-1 antibody as a therapy for advanced lymphoma.2,3

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NK Cells Combined with Bispecific Antibody in CD30+ Hodgkin and non-Hodgkin Lymphoma

The experimental AMF13 “engager” combined with preactivated and expanded natural killer (NK) cells induced an overall response rate of 90% in 22 patients with relapsed or refractory CD30+ heavily pretreated lymphomas according to researchers at the University of Texas MD Anderson Cancer Center.4,5

This approach uniquely combines umbilical cord blood-derived expanded NK cells precomplexed with the engager AMF13 construct. Patients received 2 cycles of fludarabine and cyclophosphamide, followed by the AFM13-CB NK cells at 3 dose levels.

Patients were heavily pretreated, with a median of 7 (range, 1-14) prior lines of therapy. Nine had failed an autologous and 5 an allogeneic stem cell transplant. SCT. At a median follow-up of 11 months, 52% of patients survived with lymphoma and 81% survived overall. Treatment was well tolerated and there were no instances of cytokine release syndrome, no neurotoxicity or GVHD.

AMG420

AMG420 is a BiTE antibody construct drug that acts as a bridge between the BCMA portion of an antigen on the surface of a myeloma cell, and the CD3 binds to the surface of a T-cell. This bridge forms the way in which Cytotoxic T-Lymphocytes (CTLs) attack and kill the myeloma cells.

Results from the study evaluating AMG 420 in patients with relapsed/refractory multiple myeloma who had received at least two prior lines of treatment showed a 31% response rate, including seven complete responses. The response rate in patients receiving the highest dose evaluated was 70% with 86% of the responders maintaining their responses for up to 7.5 months.

Side effects at the highest doses were peripheral polyneuropathy which improved to baseline after IV immunoglobulin and corticosteroid treatment and cytokine release syndrome.

General PMF Newsletter 490

More About BiTE® Technology

Bi-specific T cell engager (BiTE®) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE® antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE® antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

Reference

  1. Blood Adv. 2019;3[16]:2491-2498
  2. ASH study results for REGN1979
  3. Nieto Y, Banerjee P, Kaur I, et al. Innate cell engager (ICE) AFM13 combined with preactivated and expanded cord blood (CB)-derived NK cells for patients with refractory/relapsed CD30+ lymphoma. Presented at: 2022 AACR Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CTPL01.

  4. Natural killer cells complexed with a bispecific antibody may provide new treatment option for patients with advanced lymphoma. News release. AACR. Published April 10, 2022. Accessed April 10, 2022.