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The study proposes a novel feedback linearization and almost disturbance decoupling control of nonlinear multiple-input-multiple-output (MIMO) systems. The goal of cancer immunotherapy is focused on eliciting an immune system response against the tumor. The study investigates a novel feedback linearization control strategy of nonlinear MIMO tumor-immune system. The main contributions of this study are to construct a control strategy such that the resulting closed-loop system is valid for any initial condition with almost disturbance decoupling performance and develop the feedback linearization design for the control of a MIMO cancer model system to improve the cancer load. The performances of drug treatment based on our proposed novel nonlinear geometric feedback control are better than some existing approaches. The numerical results derived by our method imply the tumor load to be reduced to the zero value only after more short days of drug treatment and the recurrence cycle of tumor dynamics not to be existent. All the state variables of the cancer model system can be measured using the Cellometer Auto T4 Cell Counter, programmable research micro-pump and computer with Java program in the clinical study. Electrically automatic apparatus for providing antiretroviral drugs could be constructed based on the quantification of the immune variables.