Background Advanced genome engineering and synthetic biology technologies facilitate generation of T-cell, B-cell, or NK-cell cancer immunotherapies. Sourcing and processing of apheresis-derived peripheral blood mononuclear cells and whole blood starting materials have been standardized without considering racial and ethnic differences in circulating blood T-cell, B-cell, and NK-cell concentrations. Racial and ethnic differences in these concentrations may impact required apheresis duration or whole blood volume required for optimal cell therapy manufacture.

Methods Six studies that quantified peripheral blood CD3+ T-cell, CD19+ B-cell, with or without CD16+/CD56+ NK-cell concentrations using flow cytometry in healthy individuals of different races and ethnicities were examined. Chng (2004) studied Singaporean Chinese (N=184), Malays (N=22), Indians (N=19), and Caucasians (N=9). Tsegave (1999) evaluated Ethiopian Blacks (N=142) and Dutch Caucasians (N=1,356). Valiathan (2014) profiled adolescents (N=50) and adults (N=100) from South Florida. Al Qouzi (2002) characterized Saudis in Saudi Arabia (N=209). Yaman (2005) assessed Turks in Turkey (N=220). Bartlett (1998) examined African American (AA; N=177) and Latinx (N=29) adolescents in the US. Group comparisons used unpaired t tests (GraphPad Prism 9.4.1) with P<0.05 considered significant.

Results Of 2517 subjects, T-cell, B-cell, and NK-cell concentrations were reported in 2367, 2367, and 1011 subjects, respectively. Valiathan only reported lymphocyte subset ranges. Tsegave did not report NK-cell flow cytometry for Dutch subjects. Overall means ± standard deviations for T-cells, B-cells, and NK-cells per microliter of blood were 1530±485, 290±148, and 235±201, respectively. Intergroup comparisons revealed significantly lower mean T-cell concentrations in AA and Latinx compared to all other groups. Mean B-cell concentration in AA was significantly lower than all other groups except Ethiopians, Saudis, and Latinx. Mean B-cell concentration in Latinx was significantly lower than all other groups except Ethiopians, Saudis, Turks, and AA. For NK-cells, AA and Latinx had significantly lower mean concentrations than all other groups with available data. Based on standard deviations, intra-group variability was marked.

Conclusions In the absence of baseline lymphocyte subset concentration determinations, one cannot accurately predict the volume of apheresis product or whole blood required to consistently and compliantly manufacture a potentially lifesaving autologous cell therapy product. Our analysis points to particular risk of product manufacture failure in eligible AA and Latinx patients who are more likely to have abnormally low or low normal range blood T-cell, B-cell, and/or NK-cell concentrations. Consideration of these individual differences may help to make advanced cellular therapies more inclusive and insure compliant and efficacious product manufacture for all.