Fetal-maternal microchimerism: A potential novel approach for treating malignancy?

Abstract

2565 Background: Fetal-maternal microchimerism [MC] occurs during gestation or delivery, as cells traffic from the fetal circulation to the maternal circulation (and vice versa) via the placenta, and persist for decades post-partum. The reported incidence of MC is 33% in normal parous women. Methods: To explore the incidence and extent of MC among normal females and cancer patients for potential therapy, we obtained blood samples from 165 normal parous women, and 26 parous cancer patients. 31 non-parous women served as controls. The presence of male DNA was detected using two rounds of PCR with nested sets of primers specific for the Y chromosome. The sensitivity of the assay was validated at 1 male cell per 1 million female cells using DNA prepared from serial dilutions of (male) KG-1 cells in (female) K562 cells. Results: The observed frequency of MC was dependent on the amount of DNA assayed: with 1 ug DNA [∼300,000 genomes] per test, the frequency of MC was 18%. At 5 ug DNA [1.5 million genomes], this rose to 45%, and at ≥ 25 ug DNA [7.5 million genomes], 64% of normal parous women had MC. Among parous cancer patients, MC was present at 20% with 5 ug DNA, rose to 65% when ≥ 25 ug DNA or more was tested. One interesting result is that 14 out of 16 female cancer patients who had hematologic malignancies [leukemia, myeloma, CLL and NHL] were MC, while only 3 of 10 female patients with solid tumors [breast, uterine, ovarian, colon and lung cancer] were MC. 2 out the 31 normal non-parous donors were MC; this number did not increase when more DNA was assayed. The reason for the MC among non-parous subjects is unclear. We have developed a system to assess immunological tolerance in MC females, and are in the process of testing whether normal MC females are tolerant of their male offspring. Conclusions: Our results indicate the MC is much more frequent among parous women than previously reported. Provided that MC confers long-lasting tolerance of fetal tissue antigens, which we should be able to document, this suggests that son-to-mother cellular therapy may be a feasible approach for treatment of malignancy. No significant financial relationships to disclose.