B2M and neoplasm: While highly complex, NOT gates are theoretically implementable with trispecific TCEs using dual-specificity binders: for instance, a TAAxβ2MxCD3 TCE carrying a well-designed dual-specificity β2M/CD3 binder (high affinity for β2M and low affinity for CD3) could prevent CD3 engagement against TAA+/β2M+ normal cells, while permitting engagement on TAA+/β2M- cancer cells [given that a substantial fraction of solid tumors lose β2 microglobulin via genetic or epigenetic mechanisms to evade anti-tumor immunity (176)].