Bispecific antibodies, the penultimate cartridge in the oncological arsenal

The penultimate cartridge against cancer is shaped like the penultimate letter of the alphabet.

Decades ago,

.

These molecules, which are already familiar to us after years of pandemic, are 'Y'-shaped proteins that float through our body in search of their destination (the antigen), either on the surface of a bacterium, in the receptor in a virus or a tumor cell.

Science managed to reproduce them artificially (so-called monoclonal antibodies) and direct them to a target that had a therapeutic interest.

In this way, a whole range of treatments against cancer and various autoimmune diseases arose.

Recently,

.

They are called bispecific or bifunctional antibodies.

Among its advantages, it stands out that they can take by the hand a cell of the immune system, such as the T lymphocyte, to a tumor cell and in this way, kill it.

Bispecific antibodies

, when other available options have been exhausted.

This is what happens with certain blood or hematological cancers.

Thus, in certain classes of leukemia (for which there is one approved), lymphoma or multiple myeloma,

.

This other immunotherapy strategy consists of extracting immune cells (T lymphocytes) from the patient himself so that, once rearmed against the tumor cells, they are infused into the patient so that they act intensely against cancer.

The entire process of collecting cells from the patient, modifying them in a laboratory, and administering CAR-T therapy can take several weeks.

Paula Rodríguez, specialist in Hematology and Hemotherapy and medical coordinator of the Central Clinical Trials Unit of the Clínica Universidad de Navarra (CUN), has participated in one of the trials with bispecific antibodies for multiple myeloma whose results were presented at the last meeting of the American Society of Hematology.

"

and can be used in patients who cannot wait for CAR T therapy. The results show that the treatment is a new effective and safe alternative in patients who available treatments have been exhausted.

There are several randomized or randomized trials underway seeking to confirm these results in other populations of patients with less advanced disease."

The international phase I multicenter study in which this hematologist has participated analyzed

.

The CUN specialist points out that the drug that was administered to patients who had received various previous treatments was "capable of inducing a rate of high overall responses, with profound responses, including complete responses and with negative minimal residual disease";

the latter suggests that there is no evidence of cancer cells after treatment.

The researchers now hope to have new data with longer follow-up times and in more patients to confirm this good impression.

The hematologist Gloria Iacoboni, from the Vall d'Hebron University Hospital in Barcelona, ​​has also participated in a study with another bispecific antibody, this time for

in patients who do not respond or in which the disease recurs after several attempts with various treatments.

Here

.

"73% of the group that received it had at least one year of follow-up, they were already without active treatment and relapse seems rare in those who have achieved complete remission."

In addition, in cases in which the disease was still active, the trial allowed "they to be re-treated with the same bispecific antibody and then achieved a complete remission. Follow-up is still lacking, the median is 12.6 months, but the data obtained is quite positive", the hematologist comments on the study, where it was also observed that the side effects were, in general, well tolerated.

"The most frequent was the cytokine release syndrome [which occurs as a reaction to strong activation of the immune system, and manifests itself with fever, among other symptoms].

.

At full dose, treatment consisted of 12 cycles (administered every 21 days).

"Normally, the patient is admitted for the first dose and if all goes well, subsequent doses of treatment are administered on an outpatient basis."

Gloria Iacoboni adds that "one of the big questions when comparing bispecific antibodies -which are not yet approved- with CAR-T therapy is whether the responses will be equally durable. With CAR-T cells we already have data of even five years follow-up in some of them, with durable responses in 30-40% of treated patients.Experience tells us that when aggressive lymphomas do not relapse in the first two to five years, it is rare that they do so later.With antibodies bispecific, for the moment, there is little follow-up;

In the study where he participated, another international multicenter whose results were also presented at the last meeting of the ASH, 35% of the included patients had received CAR-T therapy: "There were no significant differences in terms of the rate of complete remissions compared to patients who were not treated with CAR-T", and points out that in his center

In fact, at the American hematology meeting, this specialist presented the results of a study carried out with Spanish data to determine which treatments could work better when CAR-T therapy failed to respond, and bispecific antibodies are one of them.

The work was selected by virtue of its relevance by the scientific society among the most outstanding of the congress, a fact that, by the way, is a good example of the high quality of Spanish science.

Gloria Iacoboni reflects that "if the results that are being obtained are maintained in more advanced trial phases and culminate in approval, it is hoped that they will be added as another option to CAR-T therapy."

However, "it must also be taken into account that

. The positive thing is having more options for patients and evaluating which one is the best in each of them".

In addition to these bispecific antibodies, known in scientific jargon by the English acronym BiTE (bifunctional T-cell engagers, or functional T-cell capturer), there is another type that instead of directing one of its arms to the tumor and the other to the lymphocyte , act on two targets in the same tumor cell;

it is explored in solid tumors, such as lung tumors.

And everything indicates that research has not yet said the last word on the limit that these molecules can reach.

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