Cell Therapy of Infectious Diseases

Dear Colleagues,

CMV and EBV after Hematopoietic Stem Cell Transplantation

The infection or reactivation of latent virus infections, mainly cytomegalovirus (CMV) and Epstein–Barr virus (EBV), is a frequent event (50-80%) and remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplants (HSCTs). Healthy seropositive individuals have high frequencies of CMV- and EBV-specific CD4+ and CD8+ T cells, ranging from 0,05% to 1,6% and from 0,5 to 4% of the total T-cell population, respectively, playing a critical role in controlling in these latent viral infections. The immunosurveillance that maintains this latent virus under control is lost during the post-HSCT period. Although a pre-emptive treatment with ganciclovir or foscarnet and, more recently, prophylaxis with letermovir reduces the incidence and mortality of early CMV infections in HSCTs, it may not able to control infection due to refractory or genetic viral resistance (15-20% of patients) or complicated by myelosuppression or nephrotoxicity (6-30% of patients). Furthermore, antivirals do not address the underlying immune defect and, in fact, can also delay the recovery of virus-specific immune responses explaining multiple CMV infections.

SARS-CoV-2 Infections 

Cell therapies have been studied is several clinical trials for the treatment of COVID-19 patients. Mesenchymal stromal cells (MSCs), natural killer (NK) cells and the use of cytotoxic T lymphocytes (CTLs) are currently in phase one and two trials to test their safety and efficacy in COVID-19 patients. Although some (i.e., MSC) have shown some clinical benefit, they have also raised some issues, such as immune rejection, low numbers of cells obtained, the need for T cell expansion under GMP conditions and lack of standardized protocols. NK cells from the innate immune system and T-cell-adaptive immune response are key in eliminating viral infections and controlling the disease; usually, low lymphocyte counts are present in individuals who die of COVID-19. T cell functionality is crucial for killing target infected cells. Adoptive cell therapy with HLA-matched CD45RA^- memory T cells from recovered donors has proved its efficiency in preventing infections in the field of HSCTs as well as SARS-CoV-2 infections.

Fungi and Others

CD45RA- T memory lymphocytes from allogeneic donors were found to also recognize Aspergillus and other fungi.

Adoptive Immunotherapy is a treatment option for unmet medical needs that were investigated and improved on in the last decade. HLA-matched donor lymphocyte infusion demonstrated efficacy in treating COVID-19, EBV, CMV, etc.

This Special Issue aims to review the state-of-the art when using cellular medicaments to treat infections.

Prof. Dr. Bernat Soria
Collection Editor

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